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FDA Consumer Magazine
VOL. 31 NO. 4 (MAY-JUNE 1997)
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Features

Label Literacy for OTC Drugs 
If you can't understand, or even find, all the precautions and
instructions on a bottle of cough syrup or pain reliever, FDA's proposed
medicine facts panel may be the answer.

CFC-Free Medication for an Ailing Ozone Layer 
Protect the environment or provide life-saving drugs? FDA proposes to
solve that dilemma with the phaseout of chlorofluorocarbon-containing
medical products, but not until safe and effective alternatives are
available.

Lights, Camera, Telemedicine 
Putting television and medicine together used to mean nothing more than
a weekly dose of Dr. Kildare. But video cameras, cable hookups, and
computers can now help patients and doctors get medical advice from
specialists all over the country.

Today's Special: Nutrition Information 
The time has come for your favorite restaurant to spill the high-fiber
beans. FDA now requires restaurants to give customers nutrition
information about menu items with nutrition or health claims.

Reasons for Brain Tumor Increase Not Black and White 
In the United States, the number of brain tumors has doubled in the past
10 years. But early diagnosis and the right treatment can improve the
chances of recovery.

Diabetes Demands a Triad of Treatments 
Diabetics need to fight their disease with every weapon they have: diet,
exercise, drugs, and--for many--daily insulin injections. Now a new
class of drugs just approved by FDA may help some reduce or eliminate
their need for insulin injections.


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Departments



Updates 

The latest information on FDA-related issues, gathered from FDA Press
Releases, Talk Papers, and other sources.



Notebook 

A potpourri of items of interest gathered from the Federal Register and
other sources.



Investigators' Reports 

Selected cases illustrating regulatory and administrative actions--such
as inspections, recalls, seizures, and court proceedings--by FDA's
regional and district offices across the country



Summaries of Court Actions 

Cases involving seizure, criminal and injunction proceedings.



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Label Literacy for OTC Drugs

by Dixie Farley 

Information on a medicine label should be in "plain English" and larger
type and should emphasize side effects and warnings with boldface type
and bullets, a sampling of consumers told the Food and Drug
Administration. They said this would help them understand how the drug
works and would lessen their concerns about any risk from using it.

Their comments, gathered in a 1996 focus group study, as well as several
years' worth of comments from meetings with industry, health
professionals, other consumers, and interested groups, enabled FDA on
Feb. 27 to propose labeling rules for over-the-counter drugs that would
make information on the label easier to read and understand.

"We want the label to be easier to read so people will indeed read it,"
says William Gilbertson, Pharm.D., associate director for FDA's OTC drug
monographs. "And we want it to be easier to understand so people will
react correctly."

This is especially important as many new potent medicines become
available OTC, says Debra Bowen, M.D., director of FDA's division of OTC
drug products. "These are pharmacologically active agents that have side
effects, as well as beneficial effects. To use them correctly and not
get into trouble from using them, people are going to have to read the
label and make sure they're appropriately selecting and using them with
other drugs they may be taking."

Ilisa Bernstein, a senior science policy advisor with FDA's Office of
Policy, compares the proposed changes with those imposed in 1992 for
food labeling and a new public-private plan that will give patients
better prescription drug information. (See also " 'Nutrition Facts' to
Help Consumers Eat Smart" in the FDA Consumer special report Focus on
Food Labeling and "Plan Will Give Consumers Better Prescription Drug
Info" in the Updates section of the April 1997 issue.)

"Our overall goal is to ensure that consumers read the labels, choose
the product that is right for them, and use the product correctly," says
Bernstein, who coordinated the agency's efforts to develop the OTC
labeling proposal.

Knowing Proper Medicine Use: Ay, There's the Rub 

FDA rules already require OTC drug labels to include all the information
consumers need for safe and effective use. But consumers can use the
information only if they first read the entire label and understand what
they read.

Most OTC medicines are subject to rules known as monographs, which
require certain labeling information for certain types of drugs. For
example, there is an antacids monograph for all OTC antacid products.

A few products, such as Ivy Block (bentoquatam) to prevent and treat
poison ivy, are marketed under new drug applications, which require
certain information on a specific product's label. Other rules require
additional labeling information, such as the statement to keep medicine
out of children's reach.

Ensuring proper use of these medicines is no small job, as FDA points
out in the OTC labeling proposal, because:

 * There are about 100,000 OTC drug products on the market.

 * Consumers self-treat four times more health problems than doctors
   treat.

 * Sixty to 95 percent of all illnesses are initially treated with
   self-care, including self-treatment with OTC drugs.

And with health-care costs on the rise, so is the use of OTC medicines.
To save money, consumers increasingly treat common ailments themselves
instead of seeing a doctor, FDA notes.

Increased use of both prescription and OTC medicines is also partially
due to the growing population of older people, who live longer due to
improved medical care that often calls for several medicines. Experts
estimate that by the year 2000, older people will account for up to half
of all medicine use.

Unfortunately, failing eyesight often accompanies old age, putting older
people at increased risk for medicine misuse and consequent health risk
because they can't read the labels. For example, an arthritic older
person who can't see well may catch a cold and decide to use an OTC
cough-cold product. If the label has tiny print and cluttered
information, the person may not be able to read that the product
contains aspirin. And if the person already takes a prescription
arthritis drug similar to aspirin, a ha

rmful effect could occur--in this instance, too much of the same type of
medicine may cause stomach or intestinal bleeding.

In reviewing studies that looked at whether people could read OTC drug
labels, FDA found one in which a significant number of people 60 and
older could not read the print on some labels because the letter width
was too compressed and the letter height too short. Another study showed
that people had to have eyesight much better than normal to read most
labels on 25 OTC drugs.

The Pharmacists Planning Service Inc., Sausalito, Calif., petitioned FDA
in the early 1990s to adopt standards for print size and style on OTC
drug labels, stating that most people can't read the small print on some
labels.

FDA's Gilbertson agrees that "to include the vast amount of information
now required for some medicines, the print could get so small some
people may not be able to read it." Required information on an aspirin
label, for example, now consists of about 500 words, he says. But about
2,000 words are required if aspirin is added to a cough-cold medicine
that also contains a cough suppressant, a nasal decongestant, and an
expectorant.

"Yet people should read the entire label," Gilbertson says, "especially
when using a medicine the first time. Some people assume if a drug is
OTC, it's 100 percent safe. Not true. All drugs pose risk. And risk
increases with improper use. If people have questions after reading the
label, they should talk to their doctor, pharmacist, or other
health-care professional."

Medicine misuse also can occur when important labeling information is
difficult to find, says FDA's Bowen.

A person allergic to an ingredient in a drug product needs to know
whether the product contains it. Although active ingredients are usually
listed on OTC drug products, current rules don't require labels for all
drugs to list inactive ingredients. And labels that do list the
information about ingredients may include it in any paragraph virtually
anywhere on the label, Bowen says. "If it's in tiny print, it's even
harder to find."

Proper use of OTC drugs becomes more critical as potent prescription
drugs increasingly switch to OTC use, as their safety profiles become
more established. (See "Now Available Without a Prescription" in the
November 1996 FDA Consumer.)

For example, Tagamet (cimetidine) and other drugs of this type are used
at prescription strength for ulcer treatment. The OTC versions, approved
only for heartburn, are at lower doses. "But Tagamet in particular can
have interactions at higher doses with other drugs," Bowen says.

FDA wants to help as many people as possible understand OTC drug labels
so they'll use the medicines properly.

The Proposed Solution 

The agency proposes an easier-to-read, easier-to-understand OTC drug
label that presents important required information as distinct elements
in an uncluttered format, using simpler wording in larger type. Most
importantly, Bowen says, "the proposal would standardize the order of
the required labeling elements and where that information is on the
label."

Standardization would eliminate current practices in which product
directions, warnings and approved uses appear in different places on the
label and the information can appear in varying type styles and with
varying graphic features. These practices make it difficult for
consumers to compare products to decide which is best for the symptoms
they wish to treat.

Confirming the need for national standards, Michael Weintraub, M.D.,
director of FDA's Office of Drug Evaluation V, says, "No matter what the
product, when a consumer in any part of the country turns over an OTC
medicine package and reads the label, we want the different types of
information to be easy to read and always in the same place. This will
increase the likelihood of safe and effective use. Consumers won't have
to hunt around anymore for information on the label."

To improve readability, FDA proposes a minimum 6-point type size for
required information. (For comparison, newspapers usually use 9- or
10-point type.)

Bowen acknowledges that "the minimum type size is not going to address
all people who have eyesight problems. But the larger type, along with a
standard location and less clutter, will help."

In its proposal, FDA asks for public comment on whether to require a
minimum type size for the principal display panel to improve readability
and to require a package insert in larger print to help ensure proper
use by people who can't read 6-point type.

Simpler, More Concise Language 

To reduce the label information load, FDA proposes simplified wording.
For example, three familiar warnings would be simplified to:

 * "If pregnant or breast-feeding, ask a health professional before use"
   instead of "As with any drug, if you are pregnant or nursing a baby,
   seek the advice of a health professional before using this product."

 * "Keep out of reach of children" instead of "Keep this and all drugs
   out of the reach of children."

 * "In case of overdose, get medical help right away" instead of "In
   case of accidental overdose, seek professional assistance or contact
   a poison control center immediately." This revision reflects the fact
   that not all states have poison control centers and that consumers
   may more readily obtain advice from more accessible medical
   professionals if the wording is changed.

Also, FDA proposes more than 35 simpler terms or phrases that can be
used on the label in lieu of more complex or technical wording. For
example, "lung" could be used instead of "pulmonary," "help" or "aid"
instead of "assistance," "use(s)" instead of "indication(s), "drug"
instead of "medication," and "hole in" instead of "perforation of."

Other changes under consideration include alternative packaging designs,
such as extending a single side panel on small packages to increase
label space, and placement of sodium, calcium, magnesium, and potassium
contents on the label.

Industry Assistance 

Last January, FDA formally recognized the Nonprescription Drug
Manufacturing Association (NDMA) for its contributions to the proposal
by presenting the group with a Special Recognition Award.

"Industry has been very forthcoming, giving us lots of good
suggestions," says FDA's Weintraub. In nominating NDMA, he commended the
group's "wholehearted effort in partnership with the agency," stating
that its members "provided excellent concepts, promoted the free and
collegial exchange of ideas with the agency, and contributed
user-friendly wording for the labels."

Said NDMA President James Cope: "Everybody benefits--particularly the
consumer--when industry and regulators strive to cooperate."

Dixie Farley is a staff writer for FDA Consumer. 


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Commenting on the Proposal

The public has until June 27 to submit written comments on FDA's
proposal for more readable labels for OTC drugs. Comments should be sent
to the FDA Dockets Management Branch, HFA-305, Room 1-23, 12420 Parklawn
Drive, Rockville, MD 20857.

FDA published its proposal in the Feb. 27, 1997, Federal Register,
available in some libraries and on the World Wide Web at
http://www.access.gpo.gov/su_docs/aces/aaces002.html. Select "Federal
Register, Volume 62 (1997)" in the list of databases, then scroll down
the page to submit this search request: "fda" and "february 27" and "otc
drugs."

After FDA reviews the comments and other submitted information, it will
issue a final rule requiring the new format on nearly all OTC drug
products. Consumers can expect to see the new labels on OTC products
about two years after that.


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Key Aspects of the Proposed OTC Drug Label

A proposed prototype label would make it easier for consumers to read,
understand and, it is hoped, follow the important information on OTC
drug labels. A comparison of the current and proposed label format can
be viewed in a 34K PDF file. The basic components of the new label are
described below.

The outline format is designed to cue consumers to the information's
organization, increasing their attention to the main messages. Other
proposed improvements include easier-to-read 6-point Helvetica type;
distinct sections presented in a standard order; and adequate spacing
between letters, words and lines of text. The required use of uppercase
and lowercase letters and dark type on a light background also would
improve readability.

 * Headings and subheadings, boldface type, bullets, and simpler,
   concise language would emphasize and clarify important information.

 * Active ingredients would be listed alphabetically with their quantity
   per dosage unit. Consumers could clearly see the purpose of each
   ingredient.

 * The list of uses in the next section would help consumers readily
   compare products to find the appropriate medicine for their specific
   symptoms.

 * Placing all warnings in one continuous space would help ensure that
   every warning noticed.

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CFC-Free Medication for an Ailing Ozone Layer

by Tamar Nordenberg 

More than 20 million Americans, including those who use metered-dose
inhalers for their asthma or chronic obstructive pulmonary disease,
could be affected if the Food and Drug Administration finalizes a policy
to phase out medical products that contain chlorofluorocarbons (CFCs).

FDA is seeking comments from the public on a rule the agency first
proposed in March that also covers CFC-containing products far less
common than metered-dose inhalers, such as nitroglycerin sprayed into
the mouth to relieve chest pain.

Metered-dose inhalers and some other medical products use CFCs as
propellants to carry the drug to the lungs or elsewhere in the body.
While these products don't present a direct threat to users' health,
they contain CFCs that eat away at the Earth's protective ozone layer
and lead to increased ultraviolet radiation reaching the Earth's
surface. Because increased UV rays are linked to skin cancer, cataracts,
suppressed immune systems, and other health problems, CFCs indirectly
can contribute to these conditions.

FDA's move toward phasing out CFC-containing medical products is part of
a worldwide reduction in CFC production under the international
agreement "Montreal Protocol on Substances that Deplete the Ozone Layer"
and the U.S. Clean Air Act. (See "Planet-Wide Phaseout.") Signed by more
than 160 countries, the protocol called for a general ban on CFC
production in industrialized countries by January 1996.

[graphic omitted shows depletion of the ozone layer over Antarctica from
1979 to 1996] >

The use of CFCs in essential medical devices, including metered-dose
inhalers, has been exempt from the ban.

"While we have an international agreement which aims for zero CFC use,
FDA will always keep in mind that millions of Americans depend on these
products to breathe," says Tunde Otulana, M.D., a medical officer with
FDA's division of pulmonary drug products and head of an agency CFC work
group. "Our goal is to protect the environment without putting patients'
health at risk."

Under the approach being considered, the sale of the remaining
CFC-containing medical products would be phased out as safe and
effective alternatives become available.

"Naturally, patients may have concerns because they will have to switch
to new medications as the products they have trusted for many years are
replaced," Otulana says. "But while the look of the non-CFC products may
be different, and the taste may be different, FDA is working to ensure
that the effectiveness and safety of the drugs will be comparable to
patients' current medications."

Public Perspective 

The agency published an "advance notice of proposed rulemaking" in the
March 6, 1997, Federal Register with a 60-day public comment period
ending May 5. The notice is available on the Government Printing
Office's web site
(http://www.access.gpo.gov/su_docs/aces/aaces002.html). Paper copies can
be obtained through FDA's fax-on-demand system by calling (1-800)
342-2722 and requesting document number 0513.

Generally, the rule in its proposed form states that CFC-containing
medical products would be considered for a phaseout once these
conditions are met:

 * Acceptable treatment alternatives exist for the particular
   metered-dose inhaler or other drug product so each patient can find a
   product that meets his or her medical needs.

 * The alternatives are marketed for at least one year and are accepted
   by patients.

 * The supply of alternative products is sufficient to ensure that there
   will be no drug shortages.

After considering the public's comments on the March notice and
incorporating changes, FDA will publish a proposed rule in the Federal
Register. The public will then have another 60 days to comment. Comments
should be sent to FDA's Dockets Management Branch, HFA-305, Room 1-23,
12420 Parklawn Drive, Rockville, MD 20857. (See "Inside FDA: How to
Comment on Proposals and Submit Petitions" in the April 1996 FDA
Consumer.)

Products with Promise 

Faced with the prospect of the eventual removal of CFC-containing
medical products from the market, companies are developing alternative
products, Otulana says.

FDA has already approved one: 3M Pharmaceuticals' Proventil HFA
(albuterol sulfate), which is marketed by Key Pharmaceuticals Inc. FDA
approved the drug in August 1996. Its active ingredient, albuterol,
remains the same as the now-marketed CFC-containing Proventil
metered-dose inhaler. But the propellant hydrofluoroalkane (HFA) carries
the drug into the lungs with no known ozone-depleting chemicals.

"[I]n the very near future there will be a whole family of HFA-propelled
products to replace the family of CFC inhalers," says Maria J. Westfall,
global program manager at 3M.

Dry powder inhalers that can hold several doses of medication are
another possible alternative to CFCs. The dry powder drug substance
would be inhaled without using any propellant.

When patients switch to the new technologies, they will understandably
have concerns, says Nancy Sander, president of the patient advocacy
organization Mothers of Asthmatics. The key to a successful transition,
she says, is to educate health-care providers and patients about the
therapeutic, as well as environmental, benefits of the switch to the new
medicines.

New technologies can have direct benefits for patients, she says.
"[Many] companies are investigating not only replacing CFC propellants
but also building a better inhaler. They could get down to pure drug in
some cases, with no additive whatsoever. Then you'd be getting more of
what you need and less of what you don't."

Most patients probably won't hesitate to switch to the new medical
products, according to a 1996 American Lung Association study. About 90
percent of patients surveyed said they would switch to a non-CFC inhaler
under a doctor's recommendation.

And patients' confidence is well-placed, Otulana says: "The policy we
are proposing will not jeopardize the availability of safe, effective
medical treatments."

Tamar Nordenberg is a staff writer for FDA Consumer. 

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Planet-Wide Phaseout

[graphic omitted illustrates the process by which chlorofluorocarbons
break down the ozone layer and the dangerous consequences that result]

CFCs (chlorofluorocarbons)--made up of fluorine, chlorine and
carbon--have been widely used in industry for decades because of the
chemicals' stability, nonflammability, and low toxicity. "The fact that
[CFCs] don't break down is a benefit for their many applications but a
curse for the stratospheric ozone," says Tom Land, environmental
protection specialist with the U.S. Environmental Protection Agency.

Because CFCs are not dissolved by rain, over the years they rise to the
ozone layer--in the stratosphere, about 10 to 20 miles (15 to 30
kilometers) above the Earth's surface. There, CFCs can linger for 100
years, while the sun's harsh radiation breaks them down, releasing
atomic chlorine. One chlorine atom can destroy more than 100,000 ozone
molecules.

Scientists have discovered that an ozone "hole" has developed over
Antarctica. The ozone levels there sometimes drop by up to 60 percent,
depending on the season, the weather, and other environmental factors.
Over the United States, as well as the rest of North America, Europe,
and Australia, ozone levels have fallen 5 to 10 percent since the 1960s,
according to EPA.

Damage to the ozone layer has dangerous consequences for humans because
the ozone molecules function as a shield from the sun's radiation,
absorbing some of the harmful ultraviolet radiation before it reaches
the Earth's surface.

Skin cancer is one of the most serious dangers from ozone depletion. A
United Nations study estimated that a 1 percent decrease in the
atmospheric ozone concentration translates into a 2 percent increase in
the rate of non-melanoma skin cancer, which can be fatal.

"If we hadn't done anything about CFCs, the depletion of the ozone would
have gotten worse, and we would have had to significantly change our
lifestyle," Land says. "We wouldn't be able to go outside without
wearing hats all the time, and we wouldn't be able to build things out
of plastic and rubber that would be exposed to sunlight because they
would deteriorate much faster."

The first move to cut back on CFCs in the United States came in the
1970s, when EPA banned use of the chemicals as aerosol propellants. But
production of CFCs grew rapidly with the discovery that they could be
used in other ways, mainly as refrigerants for air-conditioning homes
and cars, solvents for cleaning electronic equipment and precision
parts, and foam blowing agents for making foam products, such as food
service packaging.

Scientific evidence of the dangerous, rapid depletion of stratospheric
ozone led to a United Nations-sponsored international agreement, the
Montreal Protocol on Substances that Deplete the Ozone Layer. The
agreement calls for the phaseout of CFCs and other ozone-destroying
chemicals. Its goal was to virtually end CFC production in the United
States and other industrialized countries by January 1996. The timetable
allows developing countries an extra 10 years to stop making CFCs.

"Some time in the middle of the next century, the ozone layer may
recover to what is considered a normal level, as measured back in the
1960s," Land says.

As a result of worldwide efforts to protect the ozone layer, EPA expects
295 million fewer cases worldwide of non-melanoma skin cancer over the
next century.

To learn more about CFCs and the environment, call EPA's toll-free Ozone
Protection Hotline at (1-800) 296-1996, or visit the agency's web site
at http://www.epa.gov/ozone/.

--T.N. 

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Lights, Camera, Telemedicine

by Marilynn Larkin 

In Hays, Kan., an infant is born with a heart murmur. Because there is a
slight chance of severe cardiac problems when this happens, Robert Cox,
M.D., a pediatrician and medical director of rural development and
telemedicine at Hays Medical Center, seeks the advice of a cardiologist
in Kansas City, which is 270 miles away. Yet the infant and Cox never
leave the small town of Hays.

Instead, using interactive videoconferencing, the cardiologist in Kansas
City examines the infant and listens to the heartbeat as a technician in
Hays holds an instrument similar to a stethoscope against the baby's
body. The cardiologist also can view the baby's chest x-ray and
electrocardiogram. Because of this technology, Cox says, "Today, we
refer only 1 percent of infants with heart murmurs to an out-of-town
hospital, instead of 100 percent."

An elderly man who has trouble walking is referred to a small hospital
in rural West Virginia. "Even after doing a complete physical exam, no
one was sure what the problem was," recalls James Brick, M.D., a
rheumatologist and medical director of the telemedicine program at the
West Virginia University School of Medicine in Morgantown.

So a medical student at the rural hospital used videoconferencing to
present the patient's case to the chairman of the university's neurology
department. The neurologist examined the patient, put him through
various tests, and made a diagnosis of amyotrophic lateral sclerosis,
commonly known as Lou Gehrig's disease.

These doctors are practicing telemedicine, which involves the use of
computers and telecommunications equipment to provide health care over
long distances. It is actually an extension of one of the oldest,
simplest, and most popular forms of electronic medical consultation: a
telephone conversation between doctor and patient or a medical
generalist and a specialist. But, unlike the telephone, some aspects of
telemedicine are regulated by the Food and Drug Administration.

Telemedicine Technology 

Teleradiology is the oldest form of telemedicine referenced in the
medical literature and one FDA has been involved in since 1977,
according to Melvyn Greberman, M.D., of FDA's Center for Devices and
Radiological Health. As now practiced, this technology involves creating
and transmitting medical images, such as x-rays or computed tomography
scans, electronically in the form of a digital signal from one location
to another. An expert at a distant site receives the images, evaluates
them, helps make a diagno

sis, and suggests additional care as needed. The process is much like
sending an x-ray by mail or courier--but with telemedicine, the
transmission is almost instantaneous.

FDA and the medical community share responsibility for ensuring the
safety and effectiveness of the medical devices used in the telemedicine
process. For example, photographs of a suspicious skin lesion can be
sent electronically as digital images. The images are then reconstructed
for display on a monitor and read by the doctor who receives them.

"The question that the doctor should ask is, 'Is the resulting image
adequate for the purposes intended?'" FDA's Greberman says. "If an image
will be used for diagnosis, then the clinician must be certain that it
has sufficient detail to permit accurate interpretation."

For example, he says, the digitized image, which may be compressed to
reduce transmission time and storage requirements, should not have
degraded significantly in quality when it is viewed as a reconstructed
image. "FDA requires a manufacturer to indicate on-screen when
compression that results in the loss of some data is used, but the
doctor must determine the impact of this compression on the clinical
adequacy of the image," he adds.

Another form of telemedicine is interactive videoconferencing, also
known as interactive television and interactive teleconferencing. This
technique permits two doctors and a patient to confer simultaneously,
even though they are at different sites. For example, a camera in an
examining room would enable one doctor to present the patient to the
other. The other doctor, usually a consultant, also in front of a video
camera, would offer an opinion.

Nurses and other health professionals also can use interactive
television to monitor patients at home. For example, in Hays, an older
woman receives regular visits from a home health nurse via cable
television.

The woman's television emits a beep two minutes before the nurse is
scheduled to check on her. The patient switches on the television, which
also is equipped with a small videocamera. She can see the nurse, and
the nurse can see her. The nurse assesses the patient's overall
appearance; reviews her temperature, blood pressure, and other vital
signs; and reminds her to take her medication.

"With this technology, we found that one home health nurse could visit
nine patients in one morning during a blizzard, simply by working from
her base station," Kansas doctor Cox says.

The same technology also is used for educational purposes. For example,
the Georgia Telemedicine Network, which is based at the Medical College
of Georgia in Augusta, links the medical college with 44 sites
throughout the state, including the Eisenhower Army Medical Center and
Emory University Medical Center, according to Max Stachura, M.D., the
network's executive director. Medical students in remote locations take
classes at the university, doctors earn continuing medical education
credits, and health information is communicated to the public.

FDA's Role 

FDA's primary role with respect to telemedicine is to review the
devices, or hardware, before clearing them for marketing and to conduct
postmarketing surveillance--that is, to be aware of significant problems
that occur after the devices are marketed.

In July 1996, the Center for Devices and Radiological Health issued the
report "Telemedicine Related Activities." It reviews current and
potential areas of telemedicine of interest to FDA and is available on
the World Wide Web at http://www.fda.gov/cdrh/telemed.html.

Certain medical software products that may be used for diagnostic
purposes also fall under FDA's jurisdiction. However, other government
agencies--such as the Federal Communications Commission, which regulates
some aspects of the communications technologies--are involved in
telemedicine, as well. The Federal Joint Working Group on Telemedicine,
of which FDA is a participant, includes representatives from various
government agencies working together to clarify regulatory issues
related to telemedicine.

Benefits 

Telemedicine advocates believe the technology can make a critical
difference in health-care delivery in rural communities, where access to
specialized care is often sporadic and people may hesitate to travel
long distances to see a doctor. With telemedicine, experts say, patients
can benefit from the expertise of distant specialists and still receive
treatment in the community.

Kansas doctor Cox notes, for instance, that his clinic has established a
relationship with a hematologist/oncologist (a specialist in blood
diseases and cancer) at the University of Kansas Medical Center. The
specialist visits Hays twice a month, and also is available twice a week
via telemedicine. "Thus, we have a specialist available in our town
twice a week either in person or electronically," he says. "The result
is that we're able to deliver more health-care services to the
community. In addition, the 

level of quality at our local hospital is bolstered, so our staff feels
better working here. Everyone benefits."

The community benefits financially, as well, Cox says, because medical
tests and prescriptions generated by the specialist are handled locally.

The Georgia Telemedicine Network has brought similar benefits by
"empowering local practitioners," network director Stachura says. An
initial concern about telemedicine was that it would take patients away
from local primary-care doctors by moving them to larger facilities.
"But we've been able to demonstrate that 88 percent of patients seen by
specialists via telemedicine never leave their hometown," he says.

Telemedicine also can be cost-effective. In Georgia, for example,
telemedicine is used to provide services to prisoners who otherwise
would have to be transferred to health-care facilities, a move that can
be costly because of the need for guards to accompany prisoners and for
transportation. Now, according to Stachura, a mobile telemedicine van
comes to the prison on a regular basis, plugs in, and allows the
health-care professionals to give medical check-ups to inmates on site.

A cable television health-care program that is being instituted in
Georgia also can help cut health-care costs by serving as a type of
"electronic house call," both in rural communities and underserved urban
neighborhoods, Stachura notes. For example, in some instances, at-home
monitoring can delay an older person's entry into a nursing home,
resulting in improved quality of life, as well as significant cost
savings.

As the technology becomes more accepted, telemedicine could be used for
home-based follow-up care for the chronically ill, Stachura adds.
Doctors could monitor patients with diabetes or asthma at home, thus
avoiding hospitalization unless it is truly necessary. Similarly,
high-risk patients with heart problems could have their
electrocardiograms and blood pressure readings monitored at home,
forestalling the onset of more serious problems and allowing for more
cost-effective, early care.

A computerized service that could facilitate this type of care was
developed to monitor various health signs, according to a December 1996
New York Times report. The service helps patients check their blood
pressure and undergo an electrocardiogram at home, and then sends the
results via modem to a health-care provider. According to the newspaper,
the service is now in clinical trials to see whether its use can cut
down on hospital stays and emergency visits by patients with congestive
heart disease who are recovering at home.

Obstacles 

Although telemedicine offers benefits, there still are obstacles to
overcome before it becomes part of mainstream medicine, experts say.

One obstacle involves reimbursement. While Medicare and insurance
companies pay for diagnostic services such as teleradiology, most do not
yet pay for other consultative telemedicine services.

Cox joined the pediatric committee of a Kansas insurance company to help
convince company officials to provide reimbursement for telemedicine. He
argued that the technology allows doctors to take medical histories,
review scans and x-rays, diagnose problems, schedule follow-ups, and
prepare reports. "The company ultimately agreed that those components
make the consultation a reimbursable event," Cox says, adding that he
hopes other insurers will follow this precedent.

Medical licensing is another potential problem. Because telemedicine can
cross state lines, some states could require an out-of-state doctor
whose use of telemedicine crosses into their jurisdiction to get a
license in their state, even if the doctor's practice is physically
located elsewhere.

Stachura notes for instance that he sees patients from both Georgia and
South Carolina because his Georgia clinic is near the South Carolina
border. "If the patient comes to me, everything is fine," Stachura says.
"But if I use telemedicine technology to see a patient in South
Carolina--that is, if I were going to the patient, so to speak--then I
would need a license to practice medicine in South Carolina."

The licensing issue is further complicated by laws some states have
passed that prohibit out-of-state physicians from performing
telemedicine in their states, he notes.

Medical liability is an issue, as well. For example, a remote specialist
who does not perform a hands-on examination could be regarded as
delivering less-than-adequate care. Or if compressed digital images are
not reconstructed well, causing loss of valuable diagnostic information,
a doctor could possibly face a malpractice suit.

And, as in other areas, telemedicine advocates admit, the use of
technology often means that things may not run smoothly every time.
Brick recalls a time when the West Virginia telemedicine program
switched to another phone carrier. "We had people from the state
licensing board there to view the equipment, and nothing worked. We
discovered we had to reboot all the computers to make the new phone
connection."

Another time, he recalls, lightning hit a small hospital nearby and
shorted out all the computers. "It took several weeks to fix." Also, he
says, "a couple of times in the four years that we've been running the
program, the system went down while a patient was waiting on the other
end."

These technical problems notwithstanding, experts advise patients to
give telemedicine a try. "Go into it with an open mind," Brick says.
"Expect to be able to see and hear the doctor on the other end. Expect
the doctor to connect with you and personalize the experience for you.
Talk to him, ask whatever questions you have, just as you would in an
in-person consultation."

According to Stachura, it's only a matter of time before the obstacles
are overcome, and doctors and the public become more accepting of
telemedicine. "If 20 years ago, someone said you could walk up to a
machine on the street, press a few buttons and get cash or have your
financial portfolio displayed, you would have said, 'It's incredible.' "
But, like automated teller machines, he says, telemedicine eventually
will be accepted, too.

Marilynn Larkin is a medical writer in New York City. 

------------------------------------------------------------------------

Today's Special: Nutrition Information

by Paula Kurtzweil 

Remember the dieter's plate? For many years, it was the only menu item
that really catered to the health conscious among us. It usually came
with cottage cheese, several pieces of fruit, and a few crackers neatly
arranged atop a lettuce leaf. If you looked carefully, you could usually
spot it on the menu between other such fine restaurant fare as gelatin
cubes and fruit cocktail in syrup.

These days, restaurants have a lot more to offer consumers concerned
about calories and cholesterol, fat, and other nutrients that may help
reduce their risk of certain diseases. Menus now may carry items ranging
from low-fat, low-calorie tostados to full-course meals featuring
seafood or chicken dishes that are low in sodium and fat and high in
fiber and vitamins A and C. And restaurants boast about their
nutritionally modified dishes with symbols, such as a big red heart
signifying that the dish fits in w

ith a diet that is consistent with general dietary recommendations or
with claims such as "low fat," "light," or "heart healthy."

But the question is: Are these claims accurate and can they be trusted?

Regulations from the Food and Drug Administration effective May 2 are
designed to ensure that the answer is "yes." The regulations, published
in the Aug. 2, 1996, Federal Register, apply the Nutrition Labeling and
Education Act (NLEA) of 1990 to restaurant menu items that carry a claim
about the food's nutritional content or health benefits.

Under NLEA, FDA established regulations mandating specific nutrition
information on the labels of most store-bought products and set up
criteria under which nutrient and health claims can be used in food
labeling. Claims like these that appear on signs or placards in most
restaurants have been covered by the requirements of the food labeling
regulations since 1994.

The new menu regulations affect all eating establishments--whether a
small-town corner tavern or a big-city four-star restaurant, a grocery
store deli or a deli that delivers. All will have to follow requirements
for nutrition and health claims for menu items that bear a claim and
give customers the appropriate nutrition information for these items
when requested.

"The idea is for the claims to mean the same thing wherever they show
up--on food labels in the store or on menus in a restaurant," said
Michelle Smith, a food technologist in FDA's Office of Food Labeling.

Eating Out in the 1990s 

According to Smith, nutrition and health claims on menus can help people
better understand the role of diet in health and choose restaurant foods
that contribute to a healthy diet.

This is important, considering that more and more Americans are eating
their meals outside the home. According to the National Restaurant
Association, Americans spent 44 percent of their food dollars outside
the home in 1996, up from 25 percent in 1955.

According to the association's report, Tableservice Restaurant
Trends--1995, more than half of consumers 35 and older and 2 out of 5
consumers 18 to 34 look for lower fat menu options when eating out.
Also, restaurateurs report that their customers are increasingly
requesting meatless dishes.

The frequency with which eating establishments have been catering to
these preferences by making claims about menu items is not well known.
In its final rule on claims for restaurant foods, FDA cited information
from the National Restaurant Association's annual menu contest, in which
the group found that 89 percent of all printed menu entries had at least
one nutritional or health claim. But it is not known how representative
this number is for menu practices across the country.

In 1996, after a federal district court ordered FDA to include menu
claims under food labeling regulations, Bruce Silverglade, legal
director for the Center for Science in the Public Interest, said in a
press statement: "For years, many restaurant menus have made misleading
health and nutrition claims from 'low fat' claims for high-fat desserts
to claims that foods flavored with Chinese herbs will lower blood
pressure and improve vision. A restaurant menu should not be a work of
fiction." (CSPI and another public advocacy group, Public Citizen, filed
suit in 1993 against the government for excluding menu claims from the
labeling regulations.)

There are indications that interest in healthier restaurant fare is
growing. Heart Smart Restaurants, an Arizona-based company that helps
restaurants, food processors, and vending companies develop and promote
products suitable for nutrition and health claims, has seen a steady
rise in the number of its restaurant clients since the early 1990s. Judy
Peters, director of customer relations for the company, reports that the
company's restaurant clients now number in the hundreds and offer from
one to many Heart Smart dishes. The clients are located across the
country and include both single restaurants and national chains, ranging
from juice bars to steakhouses and ethnic restaurants.

Heart Smart is among a number of companies, health professionals, and
other consultants that offer such services to restaurants, usually for a
fee. Their services are not endorsed by FDA because, as a federal
agency, FDA cannot endorse any particular third-party certification
programs. 

On a smaller scale, the health, fitness and nutrition program of
Suburban Hospital in Bethesda, Md., a suburb of Washington, D.C., found
considerable interest from area restaurateurs in its Heart Healthy
Restaurant Program. This program, which helps chefs create and promote
heart-healthy foods on their menus, signed up 20 fine-dining restaurants
within a county-wide area in the first six months of its operation,
according to Linda Dolan, a registered dietitian and director of
Suburban's Well Works program. 

Many of the participating restaurants offer Italian and French cuisine.

Look to the Menu 

FDA's regulations permit restaurants to promote their healthier menu
fare using the following:

 * Specific claims about a menu item's nutrient content: for example,
   low fat or high fiber. These are known as nutrient claims.

 * Claims about the relationship between a nutrient or food and a
   disease or health condition: for example, a dish that is low in fat,
   saturated fat, and cholesterol might be able to carry a claim about
   how diets low in saturated fat and cholesterol may reduce the risk of
   heart disease. These are known as health claims, and they may
   initially appear on the menu in simple terms, such as "heart
   healthy." Further information about the claim should be available
   somewhere on the menu or in other labeling--for example, with the
   accompanying nutrition information that must be provided on request.

Consumers can use these claims to spot foods that may be more healthful
for them. They also can look for statements giving what FDA considers
general dietary guidance. For example, the salad section may start with
the message "Eating five fruits and vegetables a day is an important
part of a healthy diet." This statement would refer to the National
Cancer Institute's recommendation that Americans eat more fruits and
vegetables to help reduce their risk of cancer and heart disease.

Restaurants do not have to provide nutrition information about foods
that do not bear nutrient content or health claims or that are referred
to in general dietary guidance messages. However, restaurateurs need to
be careful that the general guidance they provide on the menu doesn't
turn into a claim, such as "Fruits and vegetables can help reduce the
risk of cancer." This, then, would require the item to meet FDA's
nutrition information and claims' requirements.

Claims that promote a nutrient or health benefit must meet certain
criteria established by FDA and the U.S. Department of Agriculture; for
example, the food must provide a requisite amount of the nutrient or
nutrients referred to in the claim. In addition, a menu item carrying a
health claim must provide significant amounts of one or more of six key
nutrients, such as vitamin C, iron or fiber, and cannot contain a food
substance at a level that increases the risk of a disease or health
condition. For example, a restaurant meal that contains 26 grams of fat
(40 percent of the Daily Value for fat) or 960 milligrams of sodium (40
percent of the Daily Value for sodium) is disqualified from making a
heart-healthy claim.

These same rules apply to claims used in the labeling of commercial food
products. But the requirements for further information differ between
restaurant and commercially manufactured foods.

To meet FDA's criteria, food manufacturers may choose to do chemical
analyses to determine the nutritional value of their products. But the
criteria for menu items are more flexible, and, under FDA's
requirements, restaurants may back up their claims with any "reasonable"
base, such as databases, cookbooks, or other secondhand sources that
provide nutrition information.

Also, restaurants do not have to provide the standard nutrition
information profile and more exacting nutrient content values required
in the Nutrition Facts panel of packaged foods. Instead, restaurants can
present the information in any format desired, and they have to provide
only information about the nutrient or nutrients that the claim is
referring to. They can say simply that the amount of the nutrient in
question does not exceed the limit imposed by FDA--for example, "This
low-fat restaurant dish provides no more than 5 grams of fat per
serving."

"It should be accurate," FDA's Smith said, "but not necessarily
precise."

Although nutrition information is not required to appear on the menu, it
must be made available to consumers when they request it. Restaurants
can present it in a printed format--such as a notebook--or by having the
staff recite it.

FDA is granting restaurants more flexibility because they don't produce
foods according to the more exacting standards that food manufacturers
follow, Smith said. She notes that restaurants change their menus
frequently and produce smaller quantities than commercial food
operations. And restaurant products often vary, depending on the type of
ingredients available.

"A commercial operation has more stability than a restaurant," she said.
"It would be an unreasonable burden to require restaurants to follow the
same labeling regulations for packaged foods."

Much of the enforcement of the menu claims' regulations will likely be
provided by state and local public health departments. The reason, Smith
said, is that state and local health departments have direct
jurisdiction over restaurants, including monitoring their food safety
and sanitation practices, and regularly visit them to ensure compliance
with various federal and state laws. Also, she said, FDA doesn't have
the resources.

Whether restaurants will continue to make claims on menus now that they
will be more closely monitored remains to be seen. "We're not sure what
the result will be," said Bob Harrington, vice president of technical
services for the National Restaurant Association. "Our fear is that the
rules are so complex and compliance so confusing that [restaurants] will
quit giving claims at all."

Healthful Foods with Flair 

But some restaurants that have added healthier menu choices highlighted
with claims report that those dishes sell well. Barbara Hartman, head
chef for Geppetto, an Italian restaurant in Bethesda, Md., and a
participant in Suburban Hospital's Heart Healthy Restaurant Program,
said the restaurant's "Healthy Menu" items account for 5 to 10 percent
of daily sales. The sandwiches--Tuna Sandwich Dijon, Grilled Vegetable
Sub, and others--represent as much as 20 percent of all sandwich sales,
she said.

"We've had an excellent response," she said. "Better than we thought we
would have."

Although most of the customer feedback has been positive, she noted that
customers sometimes complain about the blandness of the food. "There's
no salt, no sugar, no oil added," she said. "So I coach the waiters to
let customers know that the food may not be as tasty as what they're
used to. Then they won't be taken aback by what they're getting."

Healthy menu choices aren't going to appeal to every customer, either.
Heart Smart's Peters noted that one previous client, a restaurant that
offered only healthy-type foods, went out of business because its
selection was too narrow. "People need a choice," she said.

And not every dish is suitable for dietary modification. Some lose their
palatability when the fat and sodium contents are reduced to low levels,
Peters said, citing fettuccine Alfredo as a prime example. Dishes
containing cheese or cream sauces are difficult to modify, dietitian
Dolan noted. And chef Hartman said the poached salmon that used to be on
her restaurant's Healthy Menu had to be removed because the salmon
didn't fit the criteria for a "heart healthy" claim.

But there still are plenty of other dishes that can easily be used or
reworked as more healthful food offerings. Among those cited by
restaurant menu experts are grilled seafood, chicken, venison, and
ostrich; spaghetti with turkey meatballs; several Mexican dishes;
salads; and pasta dishes and other entrees traditionally made with wine
or herb sauces. Geppetto, for example, offers a single-serving
California Bambino Pizza with a whole-wheat crust, fat-reduced
mozzarella cheese, tomato basil sauce, roasted garlic, fresh mushrooms,
broccoli, and roasted peppers. It provides 506 calories, 10 grams of
fat, and 24 milligrams of cholesterol.

Tasty, yet healthful. And, one might add, a far cry from its
predecessor, the dieter's plate.

Paula Kurtzweil is a member of FDA's public affairs staff. 


------------------------------------------------------------------------

Claims Sure to Strike Menus

Nutrient Claims:

Low sodium, Low fat, Low cholesterol 

These claims mean the item contains low amounts of these nutrients.


Light 

Means the item has fewer calories and less fat than the food to which
it's being compared. (Restaurants may continue to use the term "light"
for reasons other than as a nutrient content claim--for example,
"lighter fare" to mean the dishes contain smaller portions. However, its
meaning must be clarified on the menu.)


Healthy 

Means the item is low in fat and saturated fat, has limited amounts of
cholesterol and sodium, and provides significant amounts of one or more
of the key nutrients vitamins A and C, iron, calcium, protein, or fiber. 


Health Claims:

Heart Healthy has two possible meanings: 

1.The item is low in saturated fat, cholesterol, and fat and provides
without fortification significant amounts of one or more of six key
nutrients. This claim will indicate that a diet low in saturated fat and
cholesterol may reduce the risk of heart disease. 2.The item is low in
saturated fat, cholesterol, and fat, provides without fortification
significant amounts of one or more of six key nutrients, and is a
significant source of soluble fiber (found in fruits, vegetables and
grain products). This claim will indicate that a diet low in saturated
fat and cholesterol and rich in fruits, vegetables and grain products
that contain some types of fiber (particularly soluble fiber) may reduce
the risk of heart disease.

--P.K. 


------------------------------------------------------------------------


A Roundabout Route to Menu Regulation

1990 

Congress passes the Nutrition Labeling and Education Act (NLEA), which
makes nutrition information mandatory for most foods. Among the few
foods exempted were restaurant items--unless they carried a nutrient or
health claim.



January 1993 

FDA issues regulations under NLEA that require restaurants to comply
with regulations for nutrient and health claims that appear on signs and
placards. Menu claims are exempt.



March 1993 

Two consumer advocacy groups, Public Citizen Inc. and Center for Science
in the Public Interest, file suit against the Department of Health and
Human Services and FDA, charging that the menu exemption violates NLEA
and the Administrative Procedure Act.



June 1993 

FDA proposes to require that menu items about which claims are made be
subject to the nutrient and health claims' regulations.



June 1996 

Because FDA failed to finalize its June 1993 proposal, the U.S. District
Court in Washington, D.C., rules that Congress intended restaurant menus
to be covered by NLEA and orders FDA to amend its nutrition labeling and
claims' regulations to include menu items about which claims are made.



August 1996 

FDA issues a final rule removing the restaurant menu exemption and
establishing criteria under which restaurants must provide nutrition
information for menu items.



May 2, 1997 

FDA's regulations for nutrition labeling of restaurant menu items that
bear a claim take effect. 

--P.K. 

------------------------------------------------------------------------

Reasons for Brain Tumor Increase
Not Black and White

by Evelyn Zamula 

It was a routine annual physical, and everything checked out fine. Blood
pressure normal, electrocardiogram normal, weight good, no particular
complaints--except one. The patient, 65-year-old Sylvia Zeidner of
Potomac, Md., had been having some peculiar dizzy spells, and she
laughingly told the doctor, "I must have a brain tumor."

She did. By taking her joking words seriously, the doctor saved her from
more devastating symptoms and possibly saved her life. He sent her for
an MRI, or magnetic resonance imaging, a noninvasive test approved by
the Food and Drug Administration in the early 1980s that is especially
valuable in diagnosing brain tumors. The MRI revealed a large
baseball-sized tumor sitting on top of Zeidner's brainstem, in the lower
back part of the skull.

Surgery was scheduled for a week later. The day before surgery, the
radiologist threaded a catheter--a piece of flexible rubber tubing--from
an incision in her groin up through her body to the brain and passed a
substance through the catheter that blocked the tumor's blood supply,
causing it to shrink. During the nine-hour-long operation the next day,
the surgeon successfully removed from her brain a meningioma, a type of
tumor (usually benign, not cancerous, as it was in this case) that grows
from the meni

nges, the membrane covering the brain and spinal cord. Afterwards, when
she inquired how so large a tumor could have caused so few symptoms, the
doctor replied that the tumor had grown very slowly, perhaps over 20
years. The brain had gradually accommodated the tumor's increasing size
until the pressure became too much and the brain cried out in protest.
Since the brainstem controls vital functions, such as blood pressure,
breathing and the beating of the heart, she could have died suddenly if
the tumor had grown large enough to affect those vital systems.

In the United States, about 100,000 cases of brain tumors are predicted
for 1996, almost double the number of just a decade ago. Of these, about
17,000 will originate from brain tissue and are called primary brain
tumors. Secondary (metastatic) brain tumors, those seeded by cancer
cells floating in the bloodstream from cancer of the breast, lung,
kidney, skin, or other organs, will account for the remainder. (Cancer
can spread from other parts of the body to the brain, but primary tumor
cells rarely travel outside the brain.) The incidence of brain tumors,
both primary and metastatic, appears to be increasing worldwide,
especially among the elderly, and no one is sure why.

Only Some Causes Known 

Brain tumors are abnormal growths of tissues within the skull. They can
be benign, like Sylvia's, or can be malignant, meaning cancerous. Even
benign brain tumors can be fatal when removal would damage vital brain
centers, or if they are inaccessible because they lie buried deep inside
the brain. Individuals of any age can develop brain tumors, but they
occur more frequently in older adults and in children under the age of
15. (The only form of cancer that causes more childhood deaths is
leukemia.) Certain brain tumors occur exclusively in children and
adolescents, others in adults.

The causes of primary brain tumors are unknown. Researchers so far have
not been successful in establishing a link between brain tumors and
viruses, diet, injury, hormones, certain medications, smoking, alcohol,
or other factors.

It is known that people who work with certain chemicals are at risk.
Studies have shown that some types of brain tumors occur more frequently
among workers in the oil refining, rubber manufacturing, and drug
industries and among chemists and embalmers.

Many adults treated as children decades ago for scalp ringworm with high
doses of ionizing radiation have developed brain tumors years after
exposure.

People who have impaired immunity, such as those with AIDS or those who
have undergone organ transplants, are also susceptible to brain tumors.

About 5 percent of primary brain tumors appear to be due to hereditary
factors. Sometimes, several members of the same family have brain
tumors. Certain rare inherited syndromes, such as neurofibromatosis, the
"Elephant Man" disease, increase the risk of developing a brain tumor.

Many parents whose children have developed brain tumors--and who live
near toxic waste sites or high-tension power lines--claim that exposure
to these environmental hazards is responsible for the tumors. But since
brain tumors occasionally occur in random "clusters," epidemiologists
say that studies have not been able to prove a connection between such
exposure and brain tumors.

Vague or Dramatic 

Depending on the tumor's size, type and location, symptoms can be as
vague as Sylvia's dizziness or as dramatic as the sudden seizure that
shook the left side of the body of Lee Atwater, Republican party
chairman, while he was addressing a GOP fund-raiser in 1990.

Eventually, all brain tumor symptoms get worse. Because the space inside
the skull is limited, as the tumor grows it causes increased pressure on
the brain. The tumor may also block the flow of cerebrospinal fluid, the
watery cushion that protects the brain and spinal cord from shock. In
young children, whose skulls have not yet fused, the head may enlarge in
response to this pressure, causing a condition known as hydrocephalus.

Tumors in some locations produce characteristic symptoms. For example,
tumors growing in the brain's occipital lobe, which interprets visual
images, often cause lack of vision in part of the visual field of each
eye. However, many common symptoms of brain tumors are similar to those
of other diseases (see "Distinguishing Symptoms") and can result in
misdiagnosis.

Devices Revolutionize 

The neurological examination is one of the most helpful tools in the
diagnosis of brain tumors. The neurologist checks eye movement, eye
reflexes and pupil reaction, hearing, reflexes, sensation, movement, and
balance and coordination.

Some laboratory tests, such as the electroencephalogram (EEG), are also
useful in diagnosis. The EEG uses special patches placed on the scalp to
record electrical currents. Certain patterns in the brain's electrical
activity may suggest a local abnormality. Further investigation may turn
up a tumor, stroke or other disorder.

For years, doctors diagnosed brain tumors with a technique called
angiography. A series of x-ray images is made of the brain after a "dye"
(a radiographic contrast material opaque to x-rays) is injected into a
major blood vessel. The pictures make the brain's blood vessels visible.

If angiography is not much used today, it's because the diagnosis of
brain tumors has been revolutionized in the last two decades by the
development of special imaging techniques, such as computed tomography,
or CAT scan. This test is especially useful in showing the tumor's
location. A CAT scan is made by sending x-rays through the body at
various angles and then assembling these images by computer to give
cross-sectional views. This test is often used with contrast material
injected into the patient. The dye helps outline certain parts of the
brain and sometimes makes it easier for the doctor to see abnormal
tissue, such as tumors.

Magnetic resonance imaging, or MRI, does not use x-rays, but rather
subjects tissues to a strong, but harmless and painless, magnetic field.
Unlike the CAT scan, which produces an image that depends on x-ray
absorption, MRI produces an image that reflects magnetic properties of
the body. One advantage of MRI is that the examination can be tailored
to highlight different types of diseases. MRI used in conjunction with
contrast materials containing magnetic substances (unlike those used in
CAT scans) has been found to be very effective in imaging brain tumors.

Positron emission tomography (PET) is used less often than either CAT
scanning or MRI because the equipment is more expensive. PET measures
the brain's activity using positron-emitting radiopharmaceuticals, which
are injected into the patient before the test. PET scans can be
especially useful in detecting recurrent tumors.

To make a definitive diagnosis, doctors often take a small amount of
tissue from a suspected tumor, which a pathologist examines under a
microscope. This technique, called a biopsy, can reveal whether the
cells are benign or malignant and can identify the type of tumor (there
are many different types).

Standard treatments for brain tumors include surgery, radiation therapy,
chemotherapy, or a combination of these approaches. Many benign tumors
are treated by surgery alone, resulting in a complete cure. A highly
malignant tumor, such as glioblastoma multiforme, also called high-grade
astrocytoma, may require all three types of treatment.

Surgery 

The surgeon's aim is to remove the tumor completely without damaging
normal brain tissue. To achieve this goal, a whole array of surgical
tools has been developed in recent years.

Among the most important are exquisitely miniaturized devices such as
the surgical microscope and microsurgical instruments, all regulated by
FDA. Microsurgical techniques have made it possible for the neurosurgeon
to remove tumors that were once considered inoperable.

"Surgical microscopes are continually being refined," says Steven Brem,
M.D., Chief of Neurosurgery, at the H. Lee Moffitt Cancer Center, Tampa,
Fla. "They're more flexible, more powerful, provide greater
illumination, and are easier to use. They have definitely shortened
surgical time." Magnification of the operating area has also made it
easier for the surgeon to differentiate between tumor tissue and normal
tissue.

Another tool used extensively by neurosurgeons is the ultrasonic
aspirator, a device that uses high-frequency sound waves to break up
tumors and an aspirator to "vacuum" tumor pieces. "The ultrasonic
aspirator is a safe tool that has enabled the cure of benign tumors,
especially those that are fibrous, or difficult to remove, or stuck to a
nerve," says Brem.

Lasers release a beam of concentrated light energy that can destroy
small areas of tumors and can help control bleeding. Those approved for
use on brain tumors include carbon dioxide lasers and YAG lasers (Nd:YAG
and frequency double Nd:YAG).

Radiation 

Radiation therapy is the use of high-energy beams of either x-rays or
gamma rays to stop cancer cells from growing and multiplying. Radiation
is used after surgery when the surgeon has not been able to remove every
bit of cancerous tissue, or is used instead of surgery when a tumor is
in a brain area where removal would harm the patient. Certain drugs
called radiosensitizers--HU (hydroxyurea), BUdR (bromodeoxyuridine), and
IUdR (5-iodo-2-deoxyuridine)--are sometimes given during radiation
therapy. These drugs are still being tested. It is hoped that they will
make tumor cells more sensitive to radiation therapy.

Another type of radiation treatment currently being used is interstitial
brachytherapy. Radioactive "seeds" are planted directly into the brain
tumor where they can remain for a period of time. This technique is
useful for treating small tumors that cannot be removed surgically.

Radiation destroys cancer cells, but it can also damage adjacent healthy
cells. To minimize this damage, doctors may use a special type of
radiation treatment called stereotactic radiosurgery or radiotherapy to
destroy tumors. One technique combines computer-based treatment planning
and a therapy device called the Gamma Knife. Despite its name, this
device is not a knife.

The patient is placed on a couch and is fitted with a curved steel
helmet, much like a hair dryer, but with 201 small holes. The couch
slides into a globe that beams 201 precisely focused gamma rays from
radioactive cobalt through the holes to the targeted tumor. One session
usually lasts from 15 to 45 minutes and can be repeated, if necessary.

The Gamma Knife is especially effective in shrinking or destroying
small, well-circumscribed tumors (less than one and one-quarter inches
in diameter) and tumors deep in the brainstem or in other inoperable
sites. Radiosurgery can also be used after conventional radiation
therapy to boost its effects. More than 41,000 people worldwide were
treated with the gamma knife between 1968 and 1995.

Two other machines used in stereotactic radiosurgery--the cyclotron,
used to accelerate particles, and a modified linear accelerator--also
operate on the same principle as the gamma knife: the delivery of
concentrated doses of radiation while sparing normal tissue.

Chemotherapy 

Chemotherapy uses drugs to kill tumor cells. Drugs can be given by
mouth, injected into a blood vessel or muscle, injected directly into
the cerebrospinal fluid, or infused through a catheter to arteries
supplying the brain with blood.

One stumbling block to the effectiveness of chemotherapy is the
blood-brain barrier, an elaborate network of fine blood vessels and
cells that keeps damaging substances in the blood from reaching the
brain, but can keep out beneficial drugs as well.

"An important development in the treatment of malignant brain tumors has
been the advent of intra-operative interstitial chemotherapy, which
circumvents that old bugbear, the blood-brain barrier," says Brem. "This
represents a new technology that I and many others in 45 major centers
participated in. The study, completed in 1994, was a prospective,
randomized, double-blind study [no one knew who received the placebo, or
who received the drug] in which biodegradable slow-release polymers
[Gliadel wafers] were implanted into the tumor bed after surgery. The
surgeon can remove all the gross disease, but 90 percent [of tumors]
recur within 2 centimeters. These slow-release wafers, which are
impregnated with chemotherapy--BCNU [carmustine]--have been shown to
prolong survival." Gliadel wafers are now approved for use in patients
who undergo surgery for recurrence of glioblastoma multiforme.

Doctors can treat patients who have certain types of malignant primary
brain tumors (and some benign tumors that progress despite surgery and
radiation) with chemotherapy before, during or after surgery or
radiation. Chemotherapy has been successful in young children and is
preferred in many cases to radiation, which can injure developing
brains.

The doctor must maintain a delicate balance between giving enough
chemotherapy to kill cancer cells, but not so much as to destroy healthy
cells. Drugs can be used alone, but are also used in combinations, which
are often more effective against the tumor. Other medications that do
not affect the tumor but relieve symptoms are corticosteroids to reduce
brain swelling and anticonvulsants to prevent seizures.

Cancerous tumor cells, which divide rapidly, can be killed by
chemotherapy, but some normal rapidly dividing cells, such as blood,
hair follicles, skin, and the cells lining the digestive tract, can also
be affected. That's why chemotherapy sometimes causes hair loss and
other side effects, such as nausea and vomiting, loss of appetite,
diarrhea, anemia, mouth sores, and lowered resistance to infection.

Early Diagnosis Makes a Difference 

About half of all primary brain tumors are relatively benign tumors that
can be successfully treated, according to the American Brain Tumor
Association. Many malignant tumors, including malignant primary brain
tumors, such as medulloblastoma in children, are curable by surgery,
radiation therapy, and chemotherapy. The most important predictors of a
successful outcome are early diagnosis--based on the physician's
awareness of common symptoms, as in Sylvia Zeidner's case--and proper
management of the disease by a multidisciplinary team of doctors skilled
in all phases of diagnosis and treatment.

Zeidner has been having mild headaches since her surgery a year ago, but
a recent MRI did not show any recurrence of her meningioma. The
neurosurgeon explained that the tumor's removal had left a large cavity
in her brain, which has been filling with more fluid than the brain
could absorb, thus causing the headaches.

If the headaches get worse, the excess fluid could be drained by a
shunt, a tube that is inserted into the head and then threaded under the
skin to another body cavity, most commonly the abdomen, where the fluid
drains and is absorbed.

Though implanting a shunt is a relatively minor procedure, Zeidner feels
she is not that much bothered by her headaches and has opted to treat
them with over-the-counter painkillers, which are effective, rather than
undergo another round of surgery.

Evelyn Zamula is a freelance writer in Potomac, Md. 


------------------------------------------------------------------------


Distinguishing Symptoms

Brain tumor symptoms may resemble symptoms of so many other disorders,
including stroke and less life-threatening diseases, that it may be
difficult for the doctor to make a diagnosis. For example,
headaches--the most common symptom--may be caused by sinus infections or
migraine, nausea may be due to gallbladder disease, and dizziness may be
a symptom of Menière's disease.

A CAT scan or MRI can help establish the presence of a brain tumor that
may be responsible for any of these symptoms:

 * Headaches. Meriting a visit to the doctor include headaches that are:
   worse in the morning and then improve during the day; persistent and
   accompanied by nausea and vomiting, especially sudden vomiting; and
   accompanied by double vision, weakness or numbness.

 * seizures (convulsions), especially in an adult

 * gradual loss of movement or feeling in an arm or leg

 * stumbling, unsteadiness or imbalance

 * vision or hearing loss

 * speech difficulty

 * personality changes

 * drowsiness or confusion

 * loss of memory or concentration.

--E.Z. 

------------------------------------------------------------------------


More Information

More information on brain tumors is available from:

American Brain Tumor Association
2720 River Road, Suite 146
Des Plaines, IL 60018
(1-800) 886-2282
E-mail: ABTA@aol.com
World Wide Web: http://neurosurgery.mgh.harvard.edu/abta/ 

National Brain Tumor Foundation
785 Market Street, Suite 1600
San Francisco, CA 94103
(1-800) 934-2873
E-mail: nbtf@braintumor.org
World Wide Web: http://www.braintumor.org/ 

The Brain Tumor Society
84 Seattle Street
Boston, MA 02134-1245
(1-800) 770-8287
E-mail: info@tbts.org
World Wide Web: http://www.tbts.org/ 

National Cancer Institute
Office of Cancer Communications
Room 10A-24, Building 31
Bethesda, MD 20892
(1-800) 4-CANCER [(1-800) 422-6237]
TTY: (1-800) 332-8615
World Wide Web: http://www.nci.nih.gov/ 
(information on nonmalignant tumors)

National Institute of Neurological Disorders and Stroke
Room 8A-06, Building 31
31 Center Drive
MSC 2540
Bethesda, MD 20892-2540
(1-800) 352-9424
World Wide Web: http://www.ninds.nih.gov/ 

--E.Z. 

------------------------------------------------------------------------

Diabetes Demands a Triad of Treatments

by Audrey Hingley 

Actress Mary Tyler Moore battles it. Country singer Mark Collie has it.
Rhythm and blues singer Pattie LaBelle was diagnosed with it recently.

Celebrities like Moore, Collie and LaBelle are just three well-known
faces amid the 16 million Americans suffering from diabetes mellitus, a
chronic disease in which the pancreas produces too little or no insulin,
impairing the body's ability to turn sugar into usable energy.

In recent years, the Food and Drug Administration has approved a
fast-acting form of human insulin and several new oral diabetes drugs,
including the most recent, Rezulin (troglitazone), the first of a new
class of drugs called insulin sensitizers. This drug is designed to help
Type II diabetics make better use of the insulin produced by their
bodies and could help as many as 1 million Type II diabetics reduce or
eliminate their need for insulin injections.

While it is treatable, diabetes is still a killer. The fourth leading
cause of death in America, diabetes claims an estimated 178,000 lives
each year. So the treatment is aimed at holding the disease in check,
reversing it where possible, and preventing complications.

Philip Cryer, M.D., a professor at Washington University School of
Medicine in St. Louis and president of the American Diabetes
Association, believes that most people simply don't understand the
magnitude of the diabetes problem. "Diabetes is an increasingly common,
potentially devastating, treatable yet incurable, lifelong disease. It's
the leading cause of blindness in working-age adults, the most common
cause of kidney failure leading to dialysis or transplants, and is a
leading cause of amputation," he says. "The most recent estimate we have
of diabetes' cost [in terms of] direct medical care is $90 billion
dollars annually--more than heart disease, cancer, or AIDS."

At the heart of diabetes control are dietary management and drug
treatment. The increasing emphasis on the importance of a healthy diet,
the availability of glucose monitoring devices that can help diabetics
keep a close watch over blood sugar levels, and the wide range of drug
treatments enable most diabetics to live a near-normal life.

Managing the diet is easier now because of food labeling regulations
that went into effect in 1994 (see "The New Food Label: Coping with
Diabetes" in the November 1994 FDA Consumer).

Two Types of Diabetes 

There are two main types of diabetes, Type I and Type II.
Insulin-dependent, or Type I, diabetes affects about 5 percent of all
diabetics. It's also known as juvenile diabetes because it often occurs
in people under 35 and commonly appears in children or adolescents. For
example, Mary Tyler Moore, a Type I diabetic who is international
chairman of the Juvenile Diabetes Foundation, was diagnosed in her late
20s, following a miscarriage. A routine test found her blood sugar level
was 750 milligrams per deciliter (mg/dl), as compared with the normal
level, 70 mg/dl to 105 mg/dl. And Collie has been diabetic since age 17.

In Type I diabetes, the insulin-secreting cells of the pancreas are
destroyed, with insulin production almost ceasing. Experts believe that
this may be the result of an immune response after a viral infection.

Type I diabetics must inject insulin regularly under the skin. Insulin
cannot be taken by mouth because it cannot be absorbed from the
gastrointestinal tract into the bloodstream. Doses range from one or two
up to five injections a day, adjusted in response to regular blood sugar
monitoring.

Insulin regulates both blood sugar and the speed at which sugar moves
into cells. Because food intake affects the cells' need for insulin and
insulin's ability to lower blood sugar, the diet is the cornerstone of
diabetes management: Insulin is not a replacement for proper diet.

Symptoms of untreated insulin-dependent diabetes include:

 * continuous need to urinate
 * excessive thirst
 * increased appetite
 * weakness
 * tiredness
 * urinary tract infections
 * recurrent skin infections, such as boils
 * vaginal yeast infections in women
 * blurred vision
 * tingling or numbness in hands or feet.

If Type I diabetes goes untreated, a life-threatening condition called
ketoacidosis can quickly develop. If this condition is not treated, coma
and death will follow.

Type II, or non-insulin-dependent, diabetes is the most common type. It
results when the body produces insufficient insulin to meet the body's
needs, or when the cells of the body have become resistant to insulin's
effect. While all Type I diabetics develop symptoms, only a third of
those who have Type II diabetes develop symptoms. Many people suffer
from a mild form of the disease and are unaware of it. Often it's
diagnosed only after complications are detected.

When they occur, Type II symptoms usually include frequent urination,
excessive thirst, fatigue, an increase in infections, blurred vision,
tingling in hands or feet, impotence in men, and absence of menstrual
periods in women.

Type II diabetes usually develops in people over 40, and it often runs
in families. For instance, Pattie LaBelle was diagnosed with Type II
diabetes at age 50, and her mother died of the disease.

Type II diabetes is often linked to obesity and inactivity and can often
be controlled with diet and exercise alone. Type II diabetics sometimes
use insulin, but usually oral medications are prescribed if diet and
exercise alone do not control the disease.

Malfunction in Glucose Metabolism 

In a normal body, carbohydrates (sugars and starches) are broken down in
the intestines to simple sugars (mostly glucose), which then circulate
in the blood, entering cells, where they are used to produce energy.
Diabetics respond inappropriately to carbohydrate metabolism, and
glucose can't enter the cells normally.

Insulin--a hormone that is made in the pancreas and released into the
bloodstream and carried throughout the body--enables the organs to take
sugar from the blood and use it for energy. If body cells become
resistant to insulin's effect or if there isn't enough insulin, sugar
stays in the blood and accumulates, causing high blood sugar. At the
same time, cells starve because there's no insulin to help move sugar
into the cells.

Diabetes is diagnosed by measuring blood sugar levels. This can begin
with a urine test sampled for glucose because excess sugar in the blood
spills over into the urine. Further testing involves taking blood
samples after an overnight fast. Normal fasting blood glucose levels are
between 70 mg/dl and 105 mg/dl; a fasting blood glucose measurement
greater than 140 mg/dl on two separate occasions indicates diabetes.

Diabetes can result in many complications, including nerve damage, foot
and leg ulcers, and eye problems that can lead to blindness. Diabetics
also are at greater risk for heart disease, stroke, narrowing of the
arteries, and kidney failure. But evidence shows that the better the
patient controls his or her blood sugar levels, the greater the chances
that the disease's serious complications can be reduced.

Shot of Insulin 

The first insulin for diabetes was derived from the pancreas of cows and
pigs. Today, chemically synthesized human insulin is the most often
used. It is prepared from bacteria with DNA technology. Human insulin is
not necessarily an advantage over animal insulin, and most doctors don't
recommend that patients on animal insulin automatically switch to human
insulin. But if they do switch, dosages may change. Human insulin is
preferred for those patients who take insulin intermittently.

According to Robert Misbin, M.D., medical officer for metabolic and
endocrine drug products in FDA's Center for Drug Evaluation and Research
and a practicing physician, some diabetics take beef insulin for
religious reasons because of dietary restrictions against pork. "But the
vast majority of insulin-dependent diabetics take synthesized human
insulin," he says. "Those who are taking a beef or pork insulin and
doing well--you don't necessarily change the type of insulin they take.
But for new patients I see, I would start them on human insulin."

Diabetics on intensified insulin therapy--that is, those needing
multiple daily injections or an insulin pump, which is worn 24 hours a
day--can have flexibility in when and what they eat. Other diabetics on
insulin therapy must eat at consistent times, synchronized with the
time-action of the insulin they use.

In 1996, FDA approved Humalog, which Misbin describes as "a modified
human insulin." Humalog is absorbed and dissipated more rapidly than
regular human insulin. Misbin says that Humalog is of particular benefit
to Type I diabetics who are on very strict regimens.

Julio V. Santiago, M.D., director of the Diabetes Research and Training
Center at Washington University's School of Medicine in St. Louis, notes
that Humalog is most helpful for diabetics monitoring their blood sugar
levels and taking three or more injections of insulin a day. He reports
switching most of his Type I patients who fit that profile to the new
insulin.

Oral Drugs 

Four classes of oral diabetes drugs are now available. The oldest class,
sulfonylureas (SFUs), act on the pancreatic tissue to produce insulin.
The newest one is Glimepiride, approved by FDA in 1996.

Because SFUs can become less effective after 10 or more years of use,
other drugs often are needed. Also, there is some controversy regarding
SFUs; some of these agents have been shown in studies to contribute to
increased risk of death from cardiovascular disease.

A newer class is the biguanides, including Metformin, which was approved
by FDA in 1995. This drug acts by lowering cells' resistance to insulin,
a common problem in Type II diabetes.

A third class is the alpha-glucosidase inhibitors, which include
Precose, approved by FDA in 1995, and Miglitol, approved in 1996. These
drugs slow the body's digestion of carbohydrates, delaying absorption of
glucose from the intestines.

In January 1997, FDA approved the first in a new class of diabetes
drugs, Rezulin. The new medicine helps Type II diabetics make better use
of their own insulin by resensitizing body tissues to the insulin.
Parke-Davis, a division of Warner-Lambert of Morris Plains, N.J., plans
to begin marketing the drug by summer 1997.

"It will be useful in patients who, despite taking large doses of
insulin, still are not achieving adequate glucose control," Misbin says.

Some oral drugs may be used in combination to improve blood sugar
control. For example, FDA's Misbin says, Metformin, with an SFU, is
particularly useful for Type II diabetics who are obese. "Type II
patients who would ordinarily use [only] SFUs do not gain weight with
Metformin," he explains. "[The combination] also is used for people
taking SFUs but are no longer getting the SFUs' full effect. Studies
show that when you add Metformin to a regimen of an SFU, you get a
treatment that is better than either drug used alone."

Metformin makes users more sensitive to the body's naturally produced
insulin and decreases excessive production of sugar by the liver,
another characteristic of Type II diabetes.

The drugs are not without side effects. Metformin, for example, can
cause serious cramps and diarrhea, and it can't be used in people with
kidney problems. "So if you have to go on this drug, you need to have
kidney function tests," Santiago says.

Metformin is also contraindicated in patients with liver dysfunction.
"It should be used only in healthy patients, and it's not for the
elderly," Misbin says.

Precose is less effective but usually safer to use than Metformin, he
points out. Precose's one major side effect is flatulence. Precose
stops, or delays, absorption of carbohydrates and in doing so delivers
glucose and other carbohydrates, which cause gas, Santiago explains.
"Flatulence can occur when the drug is used at high doses, but this can
be reduced by beginning the drug at a low dose and going up ... a
'start-low, go-slow' approach."

Product labeling recommends that doctors start patients on lower doses
to combat the flatulence problem.

"Although the lowest effective dose is 25 milligrams three times a day
with meals, some physicians are starting patients on just 25 mg daily to
minimize this side effect," Misbin says.

The newest drug, Rezulin, was well-tolerated in clinical studies. The
most commonly reported side effects were infection, pain and headache,
but these occurred at rates comparable to those in the placebo-treated
patients. The drug should be prescribed with caution in patients with
advanced heart failure or liver disease.

Some diabetes experts report that when it comes to prescribing initial
therapy for Type II diabetics, some doctors tend to follow a "treatment
of laziness"--for example, prescribing SFUs if they perceive
difficulties in the patient's ability to change dietary habits or
lifestyle.

"Sometimes, patients with diabetes are treated with drugs when it's not
really necessary," Misbin says. "Oral pills should be used in Type II
diabetes only when diet and exercise are not effective. It's very common
for overweight patients who lose weight to lower their own blood sugar
levels and come off the medicines. The problem is that it's very
difficult to get patients to lose weight."

So, the bottom line in diabetes control still hinges on patients'
ability to manage the disease themselves. "I don't know of a chronic
disease in which the person who suffers from it is so responsible for
its management," says ADA president Cryer. "The patient has to become an
expert regarding their own diabetes."

Although drug treatment makes a difference to many diabetics and their
quality of life, Cryer adds that current diabetes treatments are still
"not ideal." He hopes that continuing research will someday find the
answer to the diabetes dilemma.

Audrey Hingley is a writer in Mechanicsville, Va. 


------------------------------------------------------------------------


Blood Glucose Monitoring Devices

For millions of Americans with diabetes, regular home testing of blood
glucose levels is critical in controlling their disease.

"The most near-normal glucose patterns you can get will have a terrific
long-term impact on how well people with diabetes do," says Steven
Gutman, M.D., director of the division of clinical laboratory devices in
FDA's Office of Device Evaluation. But he adds, "Tight control isn't
easy because it requires multiple glucose measurements."

For many years, diabetics relied on home urine glucose testing to
monitor blood sugar levels. But the method was not without drawbacks.
Monitoring glucose levels via the urine is problematic for several
reasons: First, blood glucose concentrations above which glucose appears
in the urine vary widely among individuals, so the tests are not very
reliable. Second, factors such as fluid or vitamin C intakes can
influence test results. And third, negative tests can't distinguish
between normal, low, and moderately high blood sugar levels.

By the late 1960s, manufacturers began introducing home blood glucose
monitoring kits. These kits allowed diabetics to detect blood sugar
levels by looking at color changes on a chemical test strip using a
single drop of blood from a pricked finger. Portable meters that could
electronically read the strip and provide immediate results came along
in the late 1970s.

Although today's monitors are small, easier to use than early ones, and
reasonably priced at between $50 and $100, they all require users to
prick their fingers to provide a blood sample for testing. So diabetics
were understandably enthusiastic when a noninvasive glucose sensor
monitoring device was developed. It doesn't require a finger prick but
instead uses infrared technology to measure blood glucose. But after
reviewing data from the device's manufacturer, the Clinical Chemistry
and Clinical Toxicology Devices Advisory Panel of FDA's Medical Devices
Advisory Committee decided more data were needed to ensure the device's
safety and effectiveness.

"The idea of being able to test yourself without a painful prick is very
attractive. It would probably increase compliance because some patients
simply don't want to prick their fingers," Gutman says. "It's a very
promising technology. But you have to balance technology against
performance."

Gutman said the criteria the company chose to deem the device
successful--that 50 percent of readings agree with 20 percent of
readings from the patient's finger-prick device--was not an appropriate
target. The panel agreed that success should be defined as having 80 to
90 percent of values correlating to values obtained with finger-prick
tests. So, the FDA advisory committee also recommended that the sponsor
conduct more studies, doing them at multiple sites and involving more
women who develop diabetes while pregnant and more children. Also, the
committee suggested that the sponsor base the studies on specific study
objectives related to performance claims, with the data sufficient to
ensure safety and effectiveness.

Julio V. Santiago, M.D., an internist specializing in diabetes and a
former member of FDA's Endocrine Advisory Committee, says, "It's an
exciting new technology that diabetics could benefit from, so we were
rooting for the company. But they failed to demonstrate that the device
worked long term for home use."

Santiago says that current invasive finger-prick devices are very
reliable, with accuracy within 15 percent of real measurements 80 to 90
percent of the time. Their biggest disadvantage is cost, since each test
strip costs 50 cents, and several are often used in one day. A spokesman
for Boehringer Mannheim Corp., Rick Naples, says the cost of test strips
and lancets needed to perform self blood-glucose monitoring can average
between $600 and $1,000 a year.

Gutman says FDA appreciates the need for noninvasive glucose monitors
and is anxious to work with companies early in the development of these
devices. The Center for Devices and Radiological Health has implemented
an expedited review program for devices like noninvasive glucose
monitors so items that may be in the interest of public health can be
made available in an expedited way without compromising the devices'
safety and effectiveness, he says. "Such expedited reviews are given
precedence over routine reviews."

Gutman is optimistic about future approval of a noninvasive blood
glucose monitoring kit for diabetics. "I'd be very disappointed if we
don't eventually see a noninvasive model in the future," he says.

--A.H. 


------------------------------------------------------------------------


For More Information

Juvenile Diabetes Foundation
120 Wall St., 19th Floor
New York, NY 10005
(1-800) 533-2873)
World Wide Web: http://207.124.131.194/ 

American Diabetes Association
1660 Duke St.
Alexandria, VA 22314
(Or write to your local affiliate)
(1-800) 342-2383)
For catalog of available materials:
(1-800) 232-6733
World Wide Web: http://www.diabetes.org/ 

National Diabetes Information Clearinghouse
1 Information Way
Bethesda, MD 20892-3560
(301) 654-3327
E-mail: ndic@aerie.com

------------------------------------------------------------------------

Updates

Injuries, Deaths Linked Again to GHB Abuse

After dozens of reports of injuries, including three deaths, were linked
last year to GHB abuse, FDA has again warned that this chemical is
unapproved and potentially dangerous.

GHB (gamma hydroxybutyric acid) has been promoted as a steroid
alternative for bodybuilding and other uses for several years. (See
"Steroid Substitutes: No-Win Situation for Athletes" in the December
1992 FDA Consumer.) Recently, it has gained favor as a "recreational"
drug because of its intoxicating effects. Although GHB has undergone
clinical testing for several indications, FDA has never approved it for
sale as a medical product. It is illegal to produce or sell GHB in the
United States.

In 1990, FDA began an intense investigation of GHB distribution after
receiving reports of GHB-related illness, including vomiting, dizziness,
tremors, and seizures. Many victims required hospitalization, and some
died.

By the end of 1991, FDA and the Department of Justice had taken
enforcement action against several firms and individuals involved in
manufacturing, distributing and promoting GHB. The agency also
instituted an automatic detention policy to prevent the import of GHB
products. These actions--along with embargoes, public education
campaigns, and other federal and state measures--appeared to diminish
temporarily the distribution and abuse of GHB.

FDA has found that clandestine laboratories produced virtually all of
the chemical accounting for the recent resurgence of GHB abuse.

FDA's Office of Criminal Investigations is working with U.S. Attorneys'
offices to arrest, indict and convict individuals responsible for the
illegal operations. FDA, the Centers for Disease Control and Prevention,
and the Drug Enforcement Administration continue to monitor GHB abuse
and to develop the most effective measures to protect the public health. 

HIV Drug Approvals Increase
Options for Adults, Children 

A new protease inhibitor for treating HIV infection--not only in adults
but children, as well--has been approved by FDA. In addition, the agency
has given "pediatric use" labeling to an already approved protease
inhibitor for adults.

New protease inhibitor Viracept (nelfinavir) and the previously approved
Norvir (ritonavir) are some of the most powerful medicines against HIV,
the virus that causes AIDS.

FDA granted the approvals March 14. Viracept's approval came about three
months after FDA received the drug application. Its labeling will
include a "pediatric use" statement that gives doctors specific dosage
recommendations for patients 2 to 13.

"[These] actions not only add another powerful weapon to our arsenal for
treating HIV infection but provide us with critical information on using
these cutting edge drugs to help HIV-positive children," HHS Secretary
Donna E. Shalala said.

Viracept received "accelerated" approval, a regulatory mechanism in
which FDA bases early approval for a product on laboratory markers (such
as plasma HIV RNA, a measure of viral load) until clinical endpoints
(such as disease progression or rates of death) are available.

The drug's "pediatric use" labeling stems from a 1994 regulatory reform
measure designed to ease the process of including drug label information
to help doctors treat pediatric patients with serious or
life-threatening diseases. Pediatric labeling information can now be
included when evidence suggests that the course of the disease and
effects of a drug are similar in children and adults.

In clinical studies of up to 24 weeks, the new drug was active when used
alone or with other antiretroviral drugs for HIV. But because its
antiviral activity is increased when used with the other drugs,
combination therapy is recommended.

The most common side effect is diarrhea, which can usually be controlled
with over-the-counter medicines. Other side effects include nausea,
vomiting and weakness.

The drug cannot be used concurrently with several other drugs because of
possible drug interactions that cause serious, potentially
life-threatening irregular heartbeats or prolonged sedation. The
potential drug interactions will be clearly highlighted on the package
label.

Viracept is marketed by Agouron Pharmaceuticals, of La Jolla, Calif.
Norvir is marketed by Abbott Laboratories, of Abbott Park, Ill.

(See also "New Ways to Prevent and Treat AIDS," in the January-February
1997 FDA Consumer.) 

Dietary Supplement Rule
Under Consideration 

The question of whether FDA should establish regulations to institute
current good manufacturing practices (CGMPs) for dietary supplements is
being put forth to the public. The CGMPs would ensure that dietary
supplements are made under conditions that will result in a safe and
properly labeled product.

In an advance notice of proposed rulemaking published in the Feb. 6
Federal Register, FDA announced it would consider establishing CGMPs for
dietary supplements if public comment suggested there was a need for
such regulations. The agency also asked for comments on the kinds of
requirements the regulations ought to include.

The comment period ends May 7, 1997. Written comments can be submitted
to the Dockets Management Branch (HFA-305), Food and Drug
Administration, 12420 Parklawn Drive, Room 1-23, Rockville, MD 20857.

FDA said in the Federal Register notice that it was considering CGMP
regulations for dietary supplements because a "significant segment" of
the dietary supplement industry had told the agency that such
regulations would be helpful to ensure the products are safe for their
intended use. Also, the Dietary Supplement Health and Education Act of
1994 states that FDA may prescribe CGMPs for dietary supplements.

The notice included draft CGMPs submitted to FDA by part of the dietary
industry. FDA said the draft "provided an extremely useful starting
point should FDA decide to proceed to rulemaking." The draft CGMPs
cover, among other things, employee hygiene, disease control, building
sanitation, proper maintenance of equipment and utensils, and production
and quality control. FDA also included a series of questions on issues
of interest to the agency that were not raised in the industry
submission.

Dietary supplements include a broad spectrum of product forms and
dietary ingredients, including vitamins, minerals, herbs, amino acids,
and other substances used to supplement the diet. 

Have Your Say

The public can comment on three FDA proposals featured in this issue:

 * dietary supplements (above): deadline May 7

 * chlorofluorocarbons (CFCs) in medical products: deadline May 5

 * labeling rules for over-the-counter drugs: deadline June 27.

Shot No Longer Only Choice for Impotence Drug

An alternative form of a previously approved drug to treat impotence is
now available by prescription.

MUSE, manufactured by VIVUS Inc., Menlo Park, Calif., was approved by
FDA last Nov. 19. The product is a single-use applicator pre-filled with
a suppository of the drug alprostadil. FDA previously approved
alprostadil in injectable form under the brand name Caverject. The drug
creates an erection by relaxing the smooth muscle tissue and dilating
the major artery in the penis, which enhances blood flow to the penis.

The user inserts the applicator about one inch into the urethral opening
of the penis, where the drug is released, absorbed by the urethra, and
transported to the surrounding erectile tissues. An erection will begin
within eight to 10 minutes and may last 30 to 60 minutes. These times
will vary from patient to patient.

The most common side effects of the preparation are:

 * aching in the penis, testicles, legs, and perianum (area between the
   penis and rectum)

 * warmth or burning sensation in the urethra

 * redness of the penis due to increased blood flow

 * minor urethral bleeding or spotting.

Side effects seen less frequently are prolonged erection, swelling of
leg veins, lightheadedness or dizziness, fainting, and rapid pulse.

Female partners of men who use MUSE may have mild vaginal itching or
burning.

Men who have any of the following should not use MUSE:

 * known hypersensitivity to alprostadil
 * an abnormally formed penis
 * conditions that might result in long-lasting erections, such as
   sickle cell anemia or trait, leukemia, or multiple myeloma.

Men who have been advised not to have sex should not use MUSE. Men
should not use the product to have sexual intercourse with a pregnant
woman unless the couple uses a condom barrier.

Impotent men and their partners can contact the Impotence Institute of
America's help line at (1-800) 669-1603. (For more information on
impotence, see also "Inflatable Penile Implants Under Scrutiny" in the
January-February 1994 FDA Consumer and the article "First Impotence
Drug" accompanying "Looking for Libido Lift? The Facts About
Aphrodisiacs" in the January-February 1996 FDA Consumer.) 

Virus-Free Hemophilia B Treatment Licensed

A new biological product to prevent or control potentially
life-threatening bleeding in hemophilia B patients, including those who
need surgery, has been licensed by FDA.

The product, BeneFix (recombinant coagulation factor IX), is produced in
Chinese hamster ovary cells and, so, is free from the risk of
transmitting viruses that can contaminate human blood plasma. The
hamster cells have been modified to express the gene for the human blood
component clotting factor IX.

Hemophilia B, also called Christmas disease, affects about 3,000
Americans who cannot form blood clots adequately because of a deficiency
or defect in their clotting factor IX. Intravenous infusion of BeneFix
or highly purified factor IX product from pooled human plasma
temporarily corrects the defect.

Clinical trials showed that some hemophilia patients may need the
hamster-derived factor IX at higher doses than are needed with
plasma-derived products. During the trials, one patient developed low
levels of antibodies that neutralized the product's effect, but the
antibodies later disappeared. Another patient developed kidney damage,
which may have been related to a blood clot.

Information about the new product's use in previously untreated
hemophilia patients is limited. A clinical trial now in progress will
follow 50 such patients up to five years. The sponsor also will follow
previously treated patients for two years.

BeneFix is made by Genetics Institute, Cambridge, Mass.

(For more on hemophilia, see "Outlook Brighter for Youngsters with
Hemophilia" in the July-August 1993 FDA Consumer.) 

First Humanitarian-Use Device
Treats Fetal Urinary Blockage 

An implantable fetal bladder stent to treat urinary tract obstruction in
unborn babies is the first product approved under FDA's new rule for
humanitarian use of medical devices.

Using a needle guided by ultrasound, the doctor threads the stent
through the mother's abdomen into the bladder of the fetus. The stent,
which remains in place for the duration of pregnancy, allows urine to
drain from the fetus' bladder into the amniotic cavity. After the baby
is born, the doctor removes the stent and performs any necessary
corrective surgery.

Previous treatment consisted mainly of inserting a needle into the fetal
bladder every couple of days to drain the urine.

FDA based its Feb. 14 approval of the stent on a small clinical study by
the manufacturer, Cook OBGYN, Spencer, Ind., and on the probable
benefits from 15 years of limited use in emergency situations. Under the
new Humanitarian Device Exemption (HDE) rule, Cook may now market its
stent commercially.

The rule offers manufacturers incentives to develop devices that treat
conditions or diseases affecting fewer than 4,000 people in the United
States annually, as is true with fetal urinary tract obstruction.

To receive HDE approval for the device, Cook had to show that:

 * The stent would not expose a fetus to unreasonable risks.
 * Probable benefits outweighed probable risks.
 * No comparable treatment was available.
 * The stent could not be brought to market without an HDE.

Ordinarily, FDA requires manufacturers of new devices to provide results
of controlled clinical studies showing that their products are safe and
effective. Under the HDE rule, however, the agency exempts devices for
rare conditions from this requirement. There are two reasons: The
devices have a limited market, and the studies are often too costly for
device manufacturers, many of which are small. So, while an HDE device
must be proven safe, the manufacturer and FDA--with advice from a panel
of experts--make a judgment of "probable" benefit and allow the device
to go on the market, rather than wait for data from clinical studies to
prove effectiveness.

An HDE device may be used only in a medical facility approved by a local
institutional review board and used only for the specific rare condition
or disease for which it has been approved. HDE approval is valid for 18
months, after which it can be extended in 18-month increments if certain
criteria are met.

(See also "FDA Eases Way for Limited-Market Devices" in the "Updates"
section of the October 1996 FDA Consumer.) 

New Approach Proposed
To Regulate Human Tissue 

To allow promising medical uses of human cells and tissues to benefit
patients as soon as possible, FDA has proposed to regulate tissue
products under a new approach that bases the amount of regulation on the
degree of risk.

The agency intends to use its rulemaking process to phase in the
requirements over the next few years.

Human tissues have been used in such varied medical procedures as skin
replacement after severe burns, tendon and ligament repair after injury,
and cornea replacement for damaged eyesight. Scientists are studying
other innovative uses of human cells and tissues, including treatment of
Parkinson's disease, diabetes, and viral infections (including HIV).
Research continues into the use of "cord blood" from the placenta and
umbilical cord to treat medical conditions.

The new approach has three general goals:

 * preventing the use of contaminated tissues that could transmit
   infection

 * preventing improper handling or processing that could contaminate or
   damage tissues

 * requiring evidence of clinical safety and effectiveness for certain
   cells and tissues that may pose a relatively high risk to patients.

Novel products and extensively processed products would need FDA's
approval before marketing, while products that present a low risk would
be subject to little or no FDA regulation.

Most tissues would have to be handled according to "good tissue
practices" established by the agency.

Tissue-processing facilities would have to register with FDA and list
their products with the agency. Product labeling and promotion would
have to be clear, accurate, balanced, and not misleading.

Some tissue-related medical products are not covered by the reform
because they are regulated under existing or proposed FDA standards or
rules or by other agencies. These products include blood products for
transfusion, tissues taken from animals, human milk, collagen, and
certain types of bone marrow.

The new approach is the sixth FDA reform under the Clinton
administration's "Reinventing Government" initiative. The agency
published a notice of the reform in the March 4 Federal Register.

To obtain FDA's "Proposed Approach to Regulation of Cellular and
Tissue-Based Products," call the agency at (1-800) 835-4709 or (301)
827-1800. Or, go to http://www.fda.gov/cber/guidelines.htm on the
agency's World Wide Web site. Because the document is recent, it is near
the bottom. 

FDA Actions Against Violations in Fiscal Year 1996

The information provided here is also presented in graph format (156K
PDF document). 

 * 24,047 detentions of imported products
 * 6,418 inspectional listings of objections at firms
 * 3,015 product recalls
 * 1,035 warning letters to firms
 * 36 product seizures
 * 11 court injunctions

Free Backgrounders

Two new backgrounders are available free from FDA.

"Alpha Hydroxy Acids in Cosmetics" (BG 97-5) gives safety precautions on
using certain cosmetics. "A Handbook for Requesting Information and
Records from FDA" (BG 97-6) is an updated version of "How to Make a
Freedom of Information Act Request to FDA." 

To order single copies, write to FDA, HFI-40, Rockville, MD 20857, or
fax your order to (301) 443-9057. Include the publication number. 

------------------------------------------------------------------------

Notebook

The Notebook: a potpourri of items of interest gathered from FDA news
releases, other news sources, and the Federal Register (designated FR,
with date of publication). The Federal Register is available in many
public libraries. It is also available electronically through GPO Access
at the Government Printing Office.

The first two doses of polio vaccine children receive should be
inactivated poliovirus vaccine (IPV), which is injected, recommends the
national Centers for Disease Control and Prevention. The next two doses
should be oral poliovirus vaccine (OPV). CDC advised the measures after
more than 100 polio cases between 1980 and 1994 were linked to patients
receiving only OPV. The recommendations call for the first dose of OPV
at ages 12 to 18 months, by which time the IPV will have produced
antibodies to protect against any potential exposure to polio from the
oral vaccine. (Morbidity and Mortality Weekly Report, Jan. 31)

Dairy products must adhere to the same standards as other foods for
"lowfat" claims, FDA has confirmed. The agency denied requests for a
hearing to reevaluate a final rule published last November. Beginning
January 1998, the agency reiterated, dairy products containing more than
1 percent fat may no longer use the term "lowfat" on the label. Instead,
these products must be labeled "reduced fat." (FR Feb. 24)

The cost of marijuana as a medical expense is not tax deductible,
according to an Internal Revenue Service ruling announced Feb. 13.
Regardless of state laws, the IRS ruled, marijuana cannot be procured
legally under the Federal Controlled Substances Act and therefore may
not be deducted for medical purposes. (Internal Revenue Bulletin 1997-9,
March 3)

The first drug to prevent heartworm in cats is now available by
prescription. Heartgard for Cats (ivermectin chewables) also may be used
to remove and control certain kinds of hookworm in cats. The approved
dose is once a month in cats 6 weeks and older during the mosquito
season. An FDA final rule added the drug's Dec. 23, 1996, approval to
the agency's animal drug regulations (FR Feb. 5)

Some children still are at risk of lead exposure despite a dramatic
decline of blood lead levels in every segment of the U.S. population,
according to the national Centers for Disease Control and Prevention.
Experts believe the drop is the result of removing lead from gasoline,
as well as other sources such as household paint, food containers, and
plumbing systems. However, blood lead levels remain higher among
children in low-income families, especially those living in older
housing where leaded paints may have been used. Lead exposure in young
children is of particular concern. They absorb lead more readily than
adults and the developing nervous system is especially vulnerable to
lead's effects. For a free pamphlet, in English or Spanish, about
protecting against lead in homes, call (1-800) 424-LEAD. (Morbidity and
Mortality Weekly Report, Feb. 20)

U.S. approval of important new drugs outpaces both Germany and Japan but
is similar to the United Kingdom, according to an article published last
December in the Journal of the American Medical Association. The article
examines approval dates of 214 drugs introduced into the world market
from January 1990 through December 1994. For a free reprint of the
article, write to Office of the Commissioner (HF-1), FDA, Rockville, MD
20857.

The risk of major depression increases 2 1/2 times in women who
miscarry, according to a study by the New York State Psychiatric
Institute. The study urges doctors to monitor miscarrying women after
such a loss, especially those who are childless or have a history of
depression, and to consider referring them to a mental health
professional if needed. About a half million women miscarry annually in
the United States. (Journal of the American Medical Association, Feb. 5)

A summary of a new report on sleep medications called "The
Pharmacological Management of Insomnia" is available from the National
Sleep Foundation. To obtain the summary, send a self-addressed,
business-size envelope with 55 cents postage to the National Sleep
Foundation, 729 15th St., 4th Floor, Department FD, Washington, DC
20005. A free brochure, "When You Can't Sleep," also is available on
request.

------------------------------------------------------------------------


Investigators' Reports

Fishy Weights Net Importer Prison Term

by Dixie Farley 

Shortly after 10 p.m. on Sunday, Aug. 11, 1991, at the Houlton, Maine,
border crossing, a truck driver for a Canadian fishery backed his
tractor-trailer up to a loading dock. His cargo list showed he was
carrying 916 kilograms (2,036 pounds) of swordfish. But the fish
apparently grew in transit: According to dockside measurements by FDA
and the U.S. Customs Service, the load of fish now topped the scales at
1,560 kg (3,467 pounds).

Shortly after 2 p.m. the next day, at a Boston seafood firm, a customs
agent put his hat on, signaling to nearby FDA and customs investigators
that the firm had unloaded the fish and completed the weight sheet. They
joined the agent, who seized the mis-declared fish and the sheet that
showed the fish, at 1,528 kg (3,396 pounds), now weighed closer to what
FDA and customs had found. 

That seizure triggered a full-scale FDA investigation that last year led
to a sentence of three years and 10 months in prison, followed by three
years' supervised release, for Richard Hart, of Chatham, Mass., owner of
Seafood Enterprises Inc., Boston. He pleaded guilty to 28 counts of
fraudulent practices and false statements in importing swordfish and one
count of conspiracy. He lied about the weights of imported swordfish to
avoid FDA's required testing for methyl mercury, generally aimed at big
fish because they are the most likely to have illegal levels of the
toxin. Mercury poisoning can cause nervous system problems in humans
that may damage vision and hearing and even be fatal.

Judge D. Brock Hornby, U.S. District Court for the District of Maine,
ruled on Oct. 15, 1996, that the sentencing guideline of two to eight
months' imprisonment for Hart's offense "does not adequately reflect
harms to society." He therefore followed a more severe guideline, 46 to
57 months' imprisonment.

FDA first learned of Seafood Enterprise's illegal activities early in
August 1991, when an informant told John Ridings, an investigator with
the agency's New England district office, that Hart was importing
swordfish but lying about the weights to avoid mercury testing. The
informant said that the fish came through the Houlton port from Nova
Scotia and that a shipment was due on Sunday, Aug. 11.

On Wednesday, Aug. 7, Ridings called Seth Taylor, a special agent with
the customs office in Houlton. He asked Taylor whether he was interested
in a joint investigation. Taylor replied he was.

"I wanted to begin the operation that next Sunday," Ridings says, "and
examine every swordfish entry and weigh each swordfish destined for
Seafood Enterprises, and see what kind of weights we would come up
with." 

Around noon on the 11th, Ridings and FDA investigator Richard Vining,
now a special agent with the agency's Office of Criminal Investigations,
along with Taylor and customs supervisor William Reynolds, arrived at
the Houlton crossing to await the shipment to Hart.

At about 10:15 p.m., Brian Hubley, from B & J Fisheries, Nova Scotia,
drove in, and submitted a cargo list describing 21 fresh whole swordfish
to be delivered to Seafood Enterprises. Customs inspector David Sylvain
told Hubley to back his truck up to the loading dock.

The investigators and agents unloaded and weighed each swordfish. Only
one fish, weighing 16 kg (35 pounds), could be considered a baby
swordfish; fish this size generally contain merely a trace of mercury.
Five were quite large: 92 to 143 kg (204 to 317 pounds). But the cargo
list showed that half of the fish were babies, and not one was over 72
kg (160 pounds).

Ridings and Taylor interviewed Hubley. The driver cooperated, agreeing
to deliver his load to the Boston firm under surveillance by FDA and
customs. Taylor followed the truck, while Ridings and Vining met early
the next morning with district officials for guidance.

At about 10:30 a.m., at a motel parking lot in Boston, Vining met with
investigators Michael Marcarelli and Patricia Ronan, also with FDA's New
England district office, and Boston customs duty agent Eddie Murphy to
make final plans to seize the shipment of swordfish.

By early afternoon, the investigators had set up surveillance around the
firm. And customs agent Taylor, disguised as a passenger in Hubley's
truck, went into the firm.

Once the swordfish were unloaded and in the firm's possession, Taylor
gave the prearranged signal--putting on his hat--to summon the
surveillance team.

Murphy and Ridings met Taylor inside. Taylor identified himself to two
employees of the firm. He told them that the Customs Service had seized
the mis-declared, therefore illegal, swordfish and was now controlling
all areas where records were maintained. Taylor also seized the load's
weight sheet just completed by a company employee.

Taylor asked another employee for B & J Fisheries' records. If
necessary, he said, he would apply for a search warrant. The employee
got owner Hart on the phone.

"Hart told Taylor over the telephone that he would cooperate with us,"
Ridings says. "But a half-hour later, Taylor got a call from Hart's
attorney, who said he would advise Hart not to let us review the records
until he reviewed them first."

Without sleep now for 36 hours straight, Ridings and Taylor left for
Boston to get a search warrant. On the way, Taylor received a message to
call Hart. He did. "Hart told him there was no need for a search
warrant, that we could return to the firm and have the B & J records,"
Ridings says. "So, Taylor returned to the firm and picked up its most
recent records on B & J."

On Aug. 14, Ridings received records from the Customs Service on B & J
swordfish shipments to Seafood Enterprises. Comparing those records with
Hart's, Ridings found that in all shipments, weights on the cargo lists
were less than weights actually shipped.

That same day, at Taylor's request, Ridings and Vining returned to
Seafood Enterprises to photograph and videotape each swordfish for
evidence.

When the investigators compared the cargo lists with Hart's weight
sheets on fish received, they soon realized that some of Hart's records
were missing. Eventually, Ridings says, Hart admitted he had destroyed
records.

A lengthy investigation ensued.

"There were money laundering issues, and all kinds of leads we had to
look into," Ridings says. "It took almost a year just to gather
information and figure out what the scheme was. Also, this was an
international event because Canada is a foreign country. So we had to
get special permission to go into Canada to do interviews."

The investigators interviewed some 80 people and compiled and evaluated
records on 68 swordfish lots.

They learned that Hart's business relationship with B & J began in 1989.
At that time, Ridings says, all shipments of imported swordfish were
automatically detained at U.S. borders until the shippers could prove to
FDA that at least five of their swordfish shipments tested negative for
illegal mercury levels.

"When we looked into our records," Ridings says, "we saw that B & J had
never been able to do that. So, legally, their products were still on
automatic detention."

But in summer 1989, Hart had petitioned FDA to remove B & J from
detention, submitting as evidence records on five B & J shipments that
appeared to have acceptable mercury levels.

Unaware that the information was false, FDA took B & J off the agency's
detention list, and the fishery shipped its first truckload of swordfish
to Hart in July 1989.

"All we had to do from then on to release the B & J shipments was review
our list," Ridings says. "The manifests for every shipment showed an
average weight of fish of 85 pounds [38 kg], or baby fish. With no
significant number of large fish, there was no reason to sample for
mercury testing."

On June 13, 1995, a grand jury indicted Hart on 76 counts of fraud and
false statements in importing swordfish. The indictment also charged him
with 47 counts of money laundering related to unlawful importation.
Three days later, Hart was arrested at his Massachusetts home.

On Jan. 26, 1996, Hart pleaded guilty. Evidence showed he had smuggled
more than $4 [sic] million worth of swordfish into the United States.

B & J Fisheries agreed to cooperate in the investigation. In August
1996, in Bangor, Maine, the owner pleaded guilty to one count of entry
of goods by false means into the United States and was assessed more
than $50,000 [sic] by the U.S. Customs Service.

Dixie Farley is a staff writer for FDA Consumer. 


------------------------------------------------------------------------


Waterlogged in the West

Record flooding that shut down parts of California and Nevada for days
in January left FDA-regulated businesses--and FDA investigators--dealing
with the aftermath months later.

At press time in March, FDA investigators were continuing to assist food
companies in deciding how and which flood-drenched products could be
salvaged. Many products had been exposed to water possibly contaminated
with raw sewage and industrial chemicals.

The flooding began around Jan. 1 and was most severe in the Central
Valley of California and the Reno-Carson City, Nev., area, where various
FDA-regulated businesses--including medical device firms, drug
companies, food warehouses, and blood banks--reported losing millions of
dollars worth of products, said Ed Harris, an investigator in FDA's
Reno, Nev., resident post. Many firms did not have flood insurance, he
said.

Heavy rain and warm temperatures in the Sierra Nevada mountains, where
the snowpack was well above normal, resulted in runoff that overtaxed
area rivers, lakes and reservoirs. Up to 8 feet (2.4 meters) of water
flooded surrounding areas.

Despite sandbagging efforts, waterways overflowed, and residential and
business areas were evacuated. Roads became impassable, and in downtown
Reno, several casinos and hotels closed for the first time in years. The
Reno-Tahoe International Airport was shut down for three days. Nevada's
Truckee River peaked at a record-setting 15 feet (4.6 meters).

In the Central Valley, FDA investigators assisted state personnel in
determining product damage at FDA-related businesses. One that was
particularly hard hit was a juice concentrate firm in Marysville, Calif.
The company may have lost up to $2 million worth of products when
the Feather River overflowed and swamped the company's plant with 4 feet
(1.2 meters) of water. "Fifty-gallon drums were entirely submerged,"
said Warren Savary, leader of the district food team. "That's how high
the water was in the warehouse."

FDA and California state officials assisted the company in determining
which drums of juice concentrate could be salvaged. The concentrate was
packed inside the drums in double-layer plastic. When the river
threatened to overflow again, the company moved its salvageable
inventory to its Wapato, Wash., facility, where, in early March, FDA's
Seattle district office was monitoring the company's reconditioning
efforts.

A concern in the southern Central Valley was the safety of cauliflower
and broccoli crops in fields immersed in sewage water carried by the
flooding. This posed a risk to consumers because of possible
contamination with E. coli, hepatitis, and other human pathogens, Savary
said. This was especially a concern for cauliflower and broccoli because
they are frequently eaten raw and are not easy to clean. But, according
to Steve Kendall, compliance officer for FDA's San Francisco district
office, the crops were destroyed and could not be brought to market.

The investigators who went to Nevada assisted investigator Harris, who
runs a one-person post in Reno. Because flooding had closed the Reno
airport and the railroad to Reno, the five-member team traveled the
200-mile trip by car through the Sierra Nevada Mountains, braving what
Harris called "snowy and icy conditions along winding roads."

Once assembled in Reno, the team focused on businesses in the industrial
area of Sparks, Nev., a low-lying city next to the Truckee River. The
industrial area contains many FDA-regulated businesses, as well as
plastics and chemical companies, Harris said.

Submerged in water up to 8 feet deep, the industrial park was barricaded
for several days by public hazardous materials personnel, after
55-gallon drums and other containers of unknown substances were seen
floating in the area. Workers suspected that the drums may have
contained toxic substances used by industrial plants in the area. In
addition, two large sewer mains broke upstream.

The investigators called more than 150 FDA product-related companies to
determine the extent of flood damage. If a company spokesperson could
not be reached, the investigators put the company on an inspection list
and, once barricades were lifted, visited the company at least once in
the following seven days.

During this period, the six investigators inspected 34 food companies,
12 conveyances and support facilities for interstate airlines, five
medical device companies, and four drug firms. In addition, they
surveyed 35 other facilities for flood damage.

"The typical scene at these inspections [included] mud-covered floors,
parking lots and employees, and mountains of ruined goods--product,
furniture, equipment--piled in parking lots," Harris said. He noted that
the investigators themselves had to drive down still-flooded streets and
wade through mud to reach all the facilities.

According to Harris, the investigators helped companies segregate
useable from nonuseable products and advised them on product
reconditioning and cleanup. They coordinated their activities with the
Washoe County Health Department and the Nevada State Health Division.

Among companies experiencing significant losses were a national discount
chain's distribution center, where more than $2 million worth of
vitamins, cosmetics and food were damaged beyond use, and a device
company that lost 67 percent of its inventory of 200,000 cases of
medical examination gloves.

These and other companies were still reconditioning and assessing their
financial losses as of early March, Harris said.


--Paula Kurtzweil 


------------------------------------------------------------------------


Sandwich Maker Fined For Consent Decree Violation 

A breach in a court-ordered consent decree by a New Orleans food company
has resulted in a $2,500 [sic] fine against the company.

Finest Foods Inc., maker of "Mrs. Drake's Sandwiches," violated the
decree when it resumed operations without FDA permission after being
closed by the agency for unsanitary conditions. The 1993 consent decree
requires Finest Foods to get FDA's approval before resuming operations.

Finest Foods, which makes about 11,000 sandwiches a day for retail sale,
signed the consent decree in the U.S. District Court for the Eastern
District of Louisiana after FDA found recurring sanitation problems. A
1994 amendment to the consent decree allows FDA to shut down Finest
Foods' sandwich operation if the company violates the decree provisions.

FDA found such violations in February 1996, when investigators inspected
the facility and found Listeria monocytogenes contamination and other
conditions, such as filth in the processing plant and unsanitary food
handling procedures. L. monocytogenes can be fatal to infants, older
adults, and people with weakened immune systems. The conditions FDA
found were similar to those that led to the 1993 consent decree.

Following the February inspection, FDA sent a letter saying the plant
must cease operations until the violations are corrected.

Under the consent decree, if FDA orders the facility to shut down, the
company, with written documentation of corrections, can request
reconsideration and stay open until FDA confirms that the shutdown is
necessary. On April 23, 1996, FDA delivered another letter to Finest
Foods saying the company had failed to address its deficiencies and that
it should suspend its operations immediately. That day, the company met
with FDA and agreed to the ordered suspension.

FDA told the company that to reopen, it must:


 * shut down and clean the plant and equipment

 * hire an independent expert to ensure that the company makes the
   required corrections and to provide FDA with a written statement
   certifying compliance

 * test the plant and products for contamination.

According to court records, the company said it fulfilled all three
requirements on April 24, the day after the shutdown. But FDA learned
that the company reopened the facility before receiving test results,
without providing a written statement from the expert, and without
getting FDA's permission.

On April 30, FDA told the company it had violated the consent decree by
reopening. Finest Foods again suspended operations until May 2, when FDA
inspected the facility and allowed the company to reopen.

FDA took the consent decree breach to district court, where, on Dec. 18,
Judge Peter Beer found that the company's actions were a "willful
violation" of the decree.

In ordering the $2,500 [sic] fine, Beer cited only the company for
contempt, not the individual defendants, company owners James and
Timothy Ganus. He found that their actions "were mitigated by their
overall efforts to comply with the consent decree."

Finest Foods has since resumed operation and, FDA officials say, the
company has taken measures to stay in compliance with the consent
decree.

--John Henkel 


------------------------------------------------------------------------

Summaries of Court Actions

Summaries of Court Actions are given pursuant to Section 705 of the
Federal Food, Drug, and Cosmetic Act. Summaries of Court Actions report
cases involving seizure proceedings, criminal proceedings, and
injunction proceedings. Seizure proceedings are civil actions taken
against goods alleged to be in violation, and criminal and injunction
proceedings are against firms or individuals charged to be responsible
for violations. The cases generally involve foods, drugs, devices, or
cosmetics alleged to be adulterated or misbranded or otherwise violative
of the law when introduced into and while in interstate commerce.

Summaries of Court Actions are prepared by Food and Drug Division,
Office of the General Counsel, HHS, and are published by direction of
the Secretary of Health and Human Services.


SEIZURE ACTIONS

Food/Contamination, Spoilage, Insanitary Handling

PRODUCT: Claw crabmeat, frozen, at Belhaven, N.C. (E.D.N.C.); Civil
Action No. 4:95-CV-137-H-1.

CHARGED 12-26-95: While held for sale after shipment in interstate
commerce at Sea Safari, Ltd., in Belhaven, N.C., the article was
adulterated in that it consisted of decomposed crabmeat--402(a)(3).

DISPOSITION: A consent decree of condemnation and destruction ordered
the article destroyed. (F.D.C. No. 67117; S. No. 96-655-058; S.J. No. 1)


PRODUCT: Infant formula, at Brooklyn, N.Y. (E.D.N.Y.); Civil Action No.
CV-96-1687.

CHARGED 4-9-96: While held for sale after shipment in interstate
commerce at Sunset Merchandising, Inc., in Brooklyn, N.Y., the article
was adulterated in that it did not contain the required nutrient
inositol--412(a)(1). The article was also adulterated in that it failed
to bear a lot code--412(a)(3). The article was misbranded in that it was
represented to be for special dietary use because the label stated that
the product was infant formula--403(j). The article was also misbranded
in that the label failed to bear nutrient information, a statement of
the number of fluid ounces supplying kilocalories, a statement of the
amount of each of several nutrients supplied by 100 kilocalories, and
the weight and volume of powdered formula to be reconstituted--403(j).

DISPOSITION: A default decree of condemnation and destruction ordered
the article destroyed. (F.D.C. No. 67136; S. No. 96-752-707; S.J. No. 2)


PRODUCT: Shrimp, frozen, at Los Angeles, Calif. (C.D. Calif.); Civil
Action No. 94-4660-JSL.

CHARGED 7-12-94: While held for sale after shipment in interstate
commerce at Los Angeles Cold Storage in Los Angeles, Calif., the
articles were adulterated in that they consisted of decomposed
shrimp--402(a)(3).

DISPOSITION: A consent decree of condemnation ordered the articles
destroyed. (F.D.C. No. 66995; S. No. 94-713-500; S.J. No. 3)


PRODUCT: Shrimp, frozen, at St. Petersburg, Fla. (M.D. Fla.); Civil
Action No. 94-1386-Civ-T-23(C).

CHARGED 10-6-94: While held for sale after shipment in interstate
commerce at Sigma International, Inc., in St. Petersburg, Fla., the
articles were adulterated in that they consisted of decomposed
shrimp--402(a)(3).

DISPOSITION: The articles were reconditioned. (F.D.C. No. 67009; S. No.
94-681-792; S.J. No. 4)


PRODUCT: Smoked sprats, at Brooklyn, N.Y. (E.D.N.Y.); Civil Action No.
CV 95-2406.

CHARGED 6-14-95: While held for sale after shipment in interstate
commerce at International Gold Star Trading Company, in Brooklyn, N.Y.,
the articles were adulterated in that they were prepared and packed
under conditions whereby they might have been rendered injurious to
health--402(a)(4).

DISPOSITION: The articles were destroyed. (F.D.C. No. 67087; S. No.
94-752-104; S.J. No. 5)



Drugs/Human Use

PRODUCT: Oxygen, at Butler, Pa. (W.D. Pa.); Civil Action No. 94-620.

CHARGED 4-15-94: While held for sale after shipment in interstate
commerce at Medi-Home-Care in Butler, Pa., the articles were adulterated
in that the methods used in, and the facilities and controls used for,
their manufacture, processing, packing, and holding were not in
conformity with current good manufacturing practice
requirements--501(a)(2)(B).

DISPOSITION: A consent decree of condemnation ordered the articles
destroyed. (F.D.C. No. 66904; S. No. 93-607-839; S.J. No. 6)

PRODUCT: Oxygen, at Virginia Beach, Va. (E.D. Va.); Civil Action No.
2:96CV382.

CHARGED 4-17-96: While held for sale after shipment in interstate
commerce at Liberty Home Health Care, d/b/a Oxygen Specialties in
Virginia Beach, Va., the articles were adulterated in that the methods
used in, and the facilities and controls used for, their manufacture,
processing, packing, and holding were not in conformity with current
good manufacturing practice requirements--501(a)(2)(B). The articles
were misbranded in that their labeling failed to bear the required
statement "Caution: Federal law prohibits dispensing without
prescription"--503(b)(4).

DISPOSITION: A consent decree of condemnation ordered the articles
destroyed. (F.D.C. No. 67133; S. No. 96-703-958; S.J. No. 7)


PRODUCT: Oxygen, at Monona, Wis. (W.D. Wis.); Civil Action No.
96C-744-S.

CHARGED 8-27-96: While held for sale after shipment in interstate
commerce at Apria Healthcare, Inc., in Monona, Wis., the articles were
adulterated in that the methods used in, and the facilities and controls
used for, their manufacture, processing, packing, and holding were not
in conformity with current good manufacturing
requirements--501(a)(2)(B).

DISPOSITION: The articles were reconditioned. (F.D.C. No. 67146; S. No.
96-719-113; S.J. No. 8)


PRODUCT: Topical creams and gels, at Miami Lakes, Fla. (S.D. Fla.);
Civil Action No. 94-2507-CIV-Marcus.

CHARGED 11-23-94: While held for sale after shipment in interstate
commerce at Tex International, Inc., in Miami Lakes, Fla., the articles
were new drugs without an approved application--505(a). The articles
were misbranded in that their labels failed to bear the established
names of the drugs, and they failed to bear adequate directions for
use--502(e)(1)(A)(i) and 502(f)(1). The articles were also misbranded in
that they were not duly listed as required, and their labels failed to
bear the statement "Caution: Federal law prohibits dispensing without a
prescription"--502(o) and 503(b)(4).

DISPOSITION: A consent decree of condemnation, destruction and
re-exportation was filed. Some of the articles were destroyed, and the
others were exported to Italy. (F.D.C. No. 67030; S. No. 94-682-308;
S.J. No. 9)

Medical Devices

PRODUCT: Acu-Stop 2000, ear pieces, at Coral Springs, Fla., and Boca
Raton, Fla. (S.D. Fla.); Civil Action No. 94-7021-CIV.

CHARGED 10-21-94: While held for sale after shipment in interstate
commerce at Original Marketing, Inc., in Coral Springs, Fla., and at the
Habilitation Center for the Handicapped, in Boca Raton, Fla., the
articles were adulterated in that they were class III devices without an
approved application for premarket approval--501(f)(1)(B). The articles
were misbranded in that they were manufactured in an establishment that
was not duly registered--502(o).

DISPOSITION: A consent decree of condemnation and destruction ordered
the articles destroyed. (F.D.C. No. 66976; S. No. 94-682-497; S.J. No.
10)



CIVIL MONEY PENALTIES

DEFENDANTS: DeHaven & Associates, d/b/a SMS Services, Inc., and John K.
DeHaven, at New Orleans, La. (E.D. La.); Civil Action No. 95-1177.

CHARGED 4-13-95: The defendants failed to submit the required reports
after assembling, installing and delivering diagnostic x-ray
systems--538(a)(4). The defendants failed to repair, replace, or refund
the cost of the x-ray systems that were not in compliance--538(a)(2).

DISPOSITION: The defendants were ordered to pay $13,000 in civil
penalties and enjoined from further violations. (F.D.C. No. 66854; S.
No. 94-689-994; S.J. No. 11)



CRIMINAL ACTIONS

DEFENDANTS: BTC Corporation and Robert L. Chan, at Fairfield, Calif.
(E.D. Calif.); Criminal No. CR-S-94-080 DFL.

CHARGED 3-4-94: Count 1: Defendant Chan, a manufacturer of diagnostic
kits, willfully conspired to defraud FDA by impeding its lawful function
of regulating the manufacture and distribution of certain types of
diagnostic kits--18 U.S.C. section 371. Counts 2 and 3: Defendant Chan
knowingly caused an employee of BTC Corporation to create a laboratory
notebook that omitted all data and references to the manufacture of
certain types of diagnostic kits--18 U.S.C. sections 1001 and 2. Count
4: Defendant Chan knowingly made a material false statement to an FDA
official--18 U.S.C. sections 1001 and 2. Count 5: Defendant Chan
instructed a BTC employee to remove from its premises chemical solutions
used in the manufacture of certain types of diagnostic kits in order to
obstruct an ongoing administrative proceeding by FDA--18 U.S.C. sections
1505 and 2.

DISPOSITION: Defendant Chan pleaded guilty to count five. He was
sentenced to six months of imprisonment and 24 months of supervised
release, and was ordered to pay a $50 special assessment. (F.D.C. No.
66804; S.J. No. 12)

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