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FDA Consumer magazine (April 1996) 
VOL. 30 NO. 3  APRIL 1996
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Features

Inside FDA: How to Comment on Proposals and Submit Petitions
The law welcomes the public to participate in FDA's rule-making process.
Here are the ins and outs of two ways to convey your opinions to the
agency.

Healthful Snacks for the Chip-and-Dip Crowd
Even if you usually snack on apples and carrots, some occasions just
don't seem complete without chips, dips, and other challenges to wise
diets. But there are ways to have your chips and eat healthy, too.

New Ways to Heal Broken Bones
More than a million Americans suffer broken bones every year. Bone
grafts, bone growth stimulators, and new kinds of replacement joints are
among the treatments making recuperation easier.

Book Reopened on Infectious Diseases
Earlier this century health experts, elated by newly available vaccines
and antibiotics, felt most infectious diseases no longer posed a threat.
But some microbes have outmaneuvered modern medicine as old diseases
resurface and new ones emerge.

On the Teen Scene: An Itch Like No Other
Yeast infections are most common in young women. Medications recently
made available over-the-counter, as well as at least one new
prescription product, make it easier to end the itch before it turns
into pain. 


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Departments



Updates 

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


Consumer Forum 

Letters to the editor of FDA Consumer magazine.


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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Inside FDA:
How to Comment on Proposals
And Submit Petitions 

by John Henkel 

(This is the first article in a series on FDA activities and concerns.)

You can influence FDA actions. As a regulatory agency, FDA publishes
rules that establish or modify the way it regulates foods, drugs,
biologics, cosmetics, radiation-emitting electronic products, and
medical devices. FDA rules have considerable impact on individual
well-being and the nation's health, industries and economy. These rules
are formed with the help of the medical community, industry--and
consumers.

By law, anyone can participate in the rule-making process by commenting
in writing on rules FDA proposes. FDA allows plenty of time for public
input and carefully considers these comments when it draws up a final
rule.

FDA gathers public comments mainly through two channels: proposed rules
and petitions.

Proposed Rules 

When FDA plans to issue a new regulation or revise an existing one, it
places an announcement in the Federal Register on the day the public
comment period begins. Published every weekday, the Federal Register is
available at many public libraries and colleges, and on the Internet.
Issues open to public comment often are reported by the news media and
may frequently be found on FDA's Internet home page (see "Using the
Internet").

In the Federal Register, the "notice of proposed rulemaking" describes
the planned regulation and provides background on the issue. It also
gives the address for submitting written comments, a contact for more
information, and the deadline for public comments.

Usually, the comment period lasts at least 60 days, though some comment
periods have been as short as 10 days or as long as nine months.
Weekends and holidays are included in the comment period.

There is no special form to fill out for comments, nor do submitters
have to follow a certain style. But FDA can process comments more
effectively if they are presented--either written legibly or typed--on 8
1/2- by 11-inch paper. 

Here are some other suggestions for making effective comments:

 * Clearly indicate if you are for or against the proposed rule or some
   part of it and why. FDA regulatory decisions are based largely on law
   and science, and agency reviewers look for reasoning, logic, and good
   science in public comments.

 * Refer to the docket number, listed in the Federal Register notice.

 * Include a copy of relevant articles or other references that support
   your comments.

 * If an article or reference is in a foreign language, you must submit
   both a copy of the original document and an English translation
   verified by a qualified translator to be accurate.

 * To protect privacy when submitting medical information, delete names
   or other information that would identify patients.

 * Threats, obscenities, profanities, or material defamatory to FDA or
   the federal government may be rejected or referred to law enforcement
   officials.

 * Comments must be postmarked or delivered in person by the last day of
   the comment period.

The number of comments received for proposals have varied greatly. A
rule that established reporting procedures for problems with medical
devices attracted 300 comments, while a recent proposal to regulate
tobacco generated over 500,000 comments.

When FDA receives a comment, it is logged in, numbered, and placed in a
file for that docket. It then becomes a public record and is available
for anyone to examine in FDA's reading room (Room 1-23, 12420 Parklawn
Drive, Rockville, Md.). Under the Freedom of Information Act (FOIA),
visitors to the reading room can receive free copies of comments up to
50 pages if their request is for noncommercial use. After that, each
page costs 10 cents. People also can send FDA an FOIA request and have
copies of comments mailed to them (see "How to File a Freedom of
Information Request").

Petitions 

Another way to influence FDA is to petition the agency to issue, change
or cancel a regulation, or to take other action. The agency receives
about 200 petitions yearly.

Petitions require careful preparation by the submitter. Individuals
sometimes submit petitions, but most come from regulated industry or
consumer groups. For example, a drug company might request a change in
labeling for one of its products; a food company might ask that its
product be exempted from some provision of a regulation; or a consumer
group might petition FDA to tighten regulation of a certain product. 

Petitions submitted to FDA must contain:

 * Action requested--What rule, order, or other administrative action
   does the petitioner want FDA to issue, amend or revoke?

 * Statement of grounds--The factual and legal grounds for the petition,
   including all supporting material, and information known to the
   petitioner that may be unfavorable to the petitioner's position.

 * Certification--A statement that to the best of the petitioner's
   knowledge, the petition includes all information relevant to the
   petition, favorable or not. The petition must be signed and include
   the petitioner's address and phone number.

In addition, some petitions may require statements on:

 * Environmental impact--Generally required if the petition requests
   approval of food or color additives, drugs, biological products,
   animal drugs, or certain medical devices, or for a food to be
   categorized as GRAS (generally recognized as safe). Procedures for
   preparing environmental impact statements can be found in Title 21 of
   the Code of Federal Regulations, Sections 25.24 and 25.31. If an
   environmental impact statement is not required, petitions should
   include a statement to that effect.

 * Economic impact--Required only if FDA requests it after review of the
   petition.

Petitions should be mailed or delivered to: Dockets Management Branch,
FDA, Room 1-23, 12420 Parklawn Drive, Rockville, MD 20857.

Ultimately, FDA management decides whether to grant a petition. But
first, agency staffers evaluate it, a process that may take several
weeks to more than a year, depending on the issue's complexity. After
FDA grants or denies the petition, the agency notifies the petitioner
directly. If not satisfied, the petitioner can take the matter to court.

For more information on submitting petitions, consult Title 21 of the
Code of Federal Regulations, Sections 10.30, 10.33, and 10.35.

Besides accepting public comments and petitions, FDA also schedules
public meetings and hearings to discuss and explain its proposals. These
usually are held with industry representatives or consumer groups, but
anyone interested may attend and, with advance notice, may comment on a
proposal. Meetings often are held in the Washington, D.C., area, but
sometimes are set in other areas across the country. Meetings for the
public to present views are announced in the Federal Register.

If you have questions about the comment, petition or hearing process,
contact the FDA Dockets Management Branch, (301) 443-7542. Hours are 9
a.m. to 4 p.m., Eastern time, Monday through Friday.

John Henkel is a staff writer for FDA Consumer. 


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How to File a Freedom of Information Act Request

You can get copies of comments on any given issue by filing a Freedom of
Information Act (FOIA) request to FDA. The request is best made by
letter, specifying exactly what material is sought. Requesters usually
should be specific about what comments they want, instead of asking for
"all comments" received on a certain proposal, which in some cases can
run thousands of pages. (Indexes of comments are available by FOIA
request as well.) 

FOIA requests should include an address and phone number and be sent to
FDA, Freedom of Information Staff (HFI-35), 5600 Fishers Lane,
Rockville, MD 20857, or faxed to (301) 443-1726. For more information,
call (301) 443-6310.

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Using the Internet

Though the Federal Register is readily available from libraries in
printed form, it also can be accessed through the Internet's World Wide
Web at two addresses:

 * http://www.access.gpo.gov/su_docs/

 * http://thorplus.lib.purdue.edu/gpo/

You also can learn about new FDA issues that are open for public comment
through the agency's News Page on its Web site at
http://www.fda.gov/opacom/hpnews.html.

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Healthful Snacks for the Chip-and-Dip Crowd

by Ruth Papazian

Any nutritionist worth her salt will recommend eating an apple or carrot
sticks if you want a healthy, nutritious snack. But can you imagine
serving crudits, tofu kabobs, and rice cakes when "the gang" comes over
to watch the big game on television? Even the most health-conscious
among us have to admit that there are times when only cookies, chips,
crackers, dips, and spreads will do.

"Snack foods are a big issue with my clients," admits Connie Diekman, a
St. Louis-based registered dietitian and spokeswoman for the American
Dietetic Association. "They want to know: 'Can I still eat them?' 'How
much can I eat?' and 'What else do I have to give up?'" Of course, if
you choose to snack on fruit or low-fat yogurt you'll get fiber, calcium
and other important nutrients your body needs. "My advice is to reach
for these types of foods first and then to munch on your favorite snack
food," says Diekman.

Naomi Kulakow, coordinator of food labeling education in the Food and
Drug Administration's Center for Food Safety and Applied Nutrition,
points out that the new food label gives consumers options to find
variety, balance and moderation--the cornerstone of a healthy diet--in
their snack food choices. "Consumers now have the information they need
to make informed choices among the foods they like--they now have a tool
to help them control portion sizes, and make dietary tradeoffs or
substitutes," she says.

Another option is products containing olestra, a fat-based substitute
for conventional fats. (See "Olestra Approved with Special Labeling.")

"When choosing snack foods, I advise my clients to figure out what is
more important to them--eating a larger portion of the reduced-fat
version or eating a smaller amount of the full-fat version," Diekman
says. "For instance, if a serving of potato chips is 1 ounce (28 grams),
there may be 16 chips per serving for the full-fat version and 30 for
the fat-free version." Diekman adds that many of her clients incorporate
their favorite snacks into their diets by giving up other things, such
as not putting dressing on their salads.

She finds that "most people are interested in a particular product
attribute--the number of calories or sodium content--and may base their
snack food choices on that one factor."

Being Upfront About Nutrients 

Many well-known brands of snack foods are now available in reduced-fat
or reduced-sodium versions so you can steer clear of nutritional land
mines without being a party pooper. However, the trick is to find lower
calorie, fat or salt versions of your favorite snacks, and to compare
the amount that makes up a portion with the amount you normally eat so
you can incorporate snack foods into your diet without overdosing on fat
and salt.

How many tortilla chips make a serving? Which has less sodium per
serving, salsa or bean dip? Does a half cup of "party mix" contain more
fat than an equal amount of mixed nuts? Thanks to the Nutrition Labeling
and Education Act of 1990, the answers to such questions can be easily
found on virtually all packaged and processed foods. Redesigned in 1994
in accordance with regulations developed jointly by FDA and the U.S.
Department of Agriculture, the food label now provides more consistent
and reliable information about:

 * nutrient claims, such as "reduced sodium" or "low fat"

 * serving size and number of servings in the package or container

 * %Daily Values, which show how much of certain nutrients a serving
   contributes to your daily diet overall

 * all ingredients, including additives, artificial colors and natural
   and artificial flavors.

"A quick, easy way to spot healthier varieties of cookies, chips and
other snack foods, is to be on the lookout for products that carry the
nutrient claims 'fat free,' 'low fat,' 'light,' 'low sodium,' 'lightly'
salted, or 'reduced' calorie, fat or sodium on the front of the
package," suggests Kulakow. "You can trust these claims because they are
among a number of descriptive terms that the government has created
precise definitions for, and all foods making such nutrient claims must
meet stringent criteria," she adds. (See "Smart and Easy.")

Real-Life Serving Sizes 

"Before the new food label regulations went into effect, a serving size
was whatever the manufacturer said it was--and many packages did not
even list this information," Diekman says. "For instance, people used to
assume that a small bag of potato chips contained a single serving. That
wasn't always true before, but it's true now. The label also alerts
consumers that a bag containing more than 2 ounces (60 g) of chips
contains more than one serving." Knowing the number of servings in a
package is important because the amount of fat, sodium or calories
listed on the label is based on serving size, she adds.

You can find the serving sizes and number of servings per package on the
Nutrition Facts panel. Serving sizes are listed in both household and
metric units--for example, 14 chips (28 g)--and are more uniform across
product lines to enable you to compare the nutrient profiles of, say,
baked potato chips and fried potato chips.

In addition, serving sizes must be based on values from government food
consumption surveys, so they bear a closer resemblance to amounts that
people typically eat. "But keep in mind that if you eat more or less of
a snack food than the serving size listed on the label, you'll have to
adjust the fat, sodium and caloric content accordingly," Diekman
cautions. That means if the serving size is 14 potato chips and you eat
28, you'll have to take into account that you've munched and crunched
twice as much fat, sodium and calories as the amounts listed on the
label.

Although it seems counterintuitive, keeping track of portion size may be
especially important when a food is low- or no-fat. Two recent studies
indicated that people who know a food is low in fat tend to either eat
more of it, or to eat more throughout the day to compensate.

"Fat-free is not calorie-free," warns Diekman. "For some reason, people
seem to think they can eat as much as they want of a food that is low in
fat or fat-free." She points out that if you cut out every ounce of fat
from your diet, but consume three times the calories, you will gain
weight.

Kulakow agrees, and points out that fat-free or low-fat versions of
snack foods often contain high amounts of added sugars or sodium to
compensate for the loss of flavor that occurs when fat is removed. So
she cautions consumers to examine the amounts of these nutrients on
fat-free and low-fat products, and to pay close attention to the
calories in a single serving to avoid concluding that fat-free is
synonymous with low in calories.

Some Valuable Information 

If you zero in on the Amount Per Serving section of the Nutrition Facts
panel, you'll be able to tell at a glance whether a snack food is high
in calories, fat, saturated fat, cholesterol, and sodium. "The top part
of the food label makes it easy to compare chip A to chip B," says
Diekman.

The first line lists the number of calories in the food, and the number
of calories from fat. For instance, when choosing a dip, the number of
calories from fat is a clue that salsa is much lower in fat than sour
cream-and-onion. If you need to watch your sodium intake, you can also
compare the sodium content of a serving of baked tortilla chips and
baked potato chips before deciding which one to toss into your shopping
cart.

In addition to listing the amounts of fat and other nutrients by weight,
the Nutrition Facts panel also gives this information as a percentage of
the Daily Value. The %Daily Value is based in part on the government's
Dietary Guidelines and is meant to show how a serving of a food fits in
with current recommendations for a healthful diet. "Many people only
look at the number of grams of fat in an individual food, but have no
sense of how it fits into the daily diet. The %Daily Value quickly lets
you know this as well as whether a food is high or low in a nutrient,
such as fat," says Kulakow.

Thus, the %Daily Value enables consumers to go beyond making individual
food choices to determine how a particular food affects the overall
diet. "For example, if you want a low- or fat-free snack, pretzels are a
great choice. But if you eat two servings, you can get as much as 54
percent of the recommended daily sodium intake. Although you're avoiding
fat, you're getting a double whammy of salt," Kulakow explains. 

Diekman comments, "If you've tried baked tortilla chips and find that
you don't like them, you may decide instead to limit the amount of fat
you get by dipping your fried tortilla chips into salsa instead of
guacamole. The %Daily Value portion of the food label allows you to make
choices that meet your dietary needs while still eating the foods you
enjoy."

At the bottom of the Nutrition Facts panel, you'll see that %Daily
Values are based on a 2,000-calorie diet. Even if you eat more or less
than 2,000 calories, the %Daily Value can serve as a useful reference to
determine whether a food is high or low in a particular nutrient.
"People know they should limit the amount of fat in their diets, but
they don't always remember the recommendation to keep fat below 30
percent of caloric intake for the day or, if they do remember, don't
know how to calculate the amount of fat they should eat in a day to stay
within this limit. With the %Daily Value, however, the label does the
math for you," Kulakow says.

The %Daily Value can also help you distinguish between two similar
products, particularly when it involves a comparative nutritional claim,
such as reduced fat. "You don't need to know the precise definition of
'low' or 'reduced.' Just look at the %Daily Value and see which is
higher or lower in the nutrient you are interested in," Kulakow advises.

"You don't have to go to extremes--cutting out all snack foods from your
diet or eating only products that are fat-free," she says. "The new food
label helps you to eat what you like and still meet nutritional
recommendations if you balance your food choices. The key is to use the
label to help you make informed choices that fit into your total daily
diet. That way education, not deprivation, can help you achieve your
dietary goals."

Ruth Papazian is a writer in New York City. 

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Smart and Easy

Today, it's easier than ever to find a version of your favorite brand or
type of snack food that is lower in fat or sodium--or both--than the
"regular" version. With a bit of comparison shopping, you'll find snack
foods you can enjoy even if you are on a restricted diet because of high
blood pressure or another medical problem. These are some of the
descriptors to look for on the front of the package:

 * fat-free: less than 0.5 grams (g) of fat per serving

 * low-fat: 3 g or less per serving (if the serving size is 30 g or less
   or 2 tablespoons or less, no more than 3 g of fat per 50 g of the food)

 * light: one-third fewer calories or half the fat of the "regular"
   version

 * low-sodium: 140 milligrams (mg) or less per serving (if the serving
   size is 30 g or less or 2 tablespoons or less, no more than 140 mg of
   sodium per 50 g of the food)

 * lightly salted: at least 50 percent less sodium per serving than the
   "regular" version

 * reduced: when describing fat, sodium or calorie content, the food
   must have at least 25 percent less of these nutrients than the
   "regular" version.

--R.P. 

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Olestra Approved with Special Labeling

Products containing olestra, a fat-based substitute for conventional
fats, are expected to start appearing on store shelves soon. FDA
approved olestra last Jan. 24 for use in certain snack foods. The agency
is requiring all products containing olestra to be labeled with specific
health information.

Procter & Gamble Co. developed olestra, which it is marketing under the
trade name Olean.

Because of its unique chemical composition, olestra adds no fat or
calories to food. Potato chips, crackers, tortilla chips, or other
snacks made with olestra will be lower in fat and calories than snacks
made with traditional fats.

Olestra may cause abdominal cramping and loose stools in some
individuals, and it inhibits the body's absorption of certain
fat-soluble vitamins and nutrients. FDA is requiring Procter & Gamble
and other manufacturers who use olestra to label all foods made with
olestra and to add essential vitamins--vitamins A, D, E, and K--to
olestra.

As a condition of approval, Procter & Gamble will conduct studies to
monitor consumption as well as studies on olestra's long-term effects.
FDA will formally review these studies in a public meeting of the Foods
Advisory Committee within 30 months from the date of olestra's approval.

The following labeling statement will be on all products made with
olestra: "This Product Contains Olestra. Olestra may cause abdominal
cramping and loose stools. Olestra inhibits the absorption of some
vitamins and other nutrients. Vitamins A, D, E, and K have been added."

Like all food additives, olestra's safety was the primary focus of FDA
evaluation. For olestra, the safety evaluation focused not only on its
toxicity, but also on the product's effects on the absorption of
nutrients and on the gastrointestinal system.

Studies of olestra indicated it may cause intestinal cramps, more
frequent bowel movements, and loose stools in some individuals. These
gastrointestinal effects do not have medical consequences. The required
labeling will give consumers needed information to discontinue the
product if appropriate.

Clinical testing also indicated that olestra absorbs fat-soluble
vitamins (vitamins A, D, E and K) from foods eaten at the same time as
olestra-containing products. Studies also demonstrated that replacing
these essential nutrients in olestra-containing snacks compensates for
this effect. This information will also be included in the product
labeling.

In addition to inhibiting the absorption of essential vitamins, olestra
reduces the absorption of carotenoids--nutrients found in carrots, sweet
potatoes, green leaf vegetables, and some animal tissue. The company's
postmarketing monitoring of olestra consumption levels and additional
studies will provide FDA with further information about olestra's
effects on the absorption of carotenoids. The role of carotenoids in
human health is not fully understood, and FDA is continuing to monitor
all available scientific research on it.

In addressing these questions, FDA evaluated more than 150,000 pages of
data on olestra, drawn from more than 150 studies. Procter & Gamble
submitted these data in its original 1987 food additive petition and in
several subsequent amendments.

In addition, FDA sought advice from outside experts through its Food
Advisory Committee. A special working group of the committee met in
public in November 1995 to review and discuss the safety questions about
olestra. The working group evaluated data presented by FDA, the company,
and organizations and individuals both opposing and supporting olestra's
approval. A clear majority of the working group agreed that all major
safety issues had been identified and addressed by the FDA review, and
that the data provided reasonable certainty that the proposed use of
olestra would be safe. A majority of the full Food Advisory Committee
reaffirmed that judgment.

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New Ways to Heal Broken Bones

by Dixie Farley 

Jacqueline Wallace, of Phoenix, sat enjoying the December 1993 holidays
at her son's home in Gaithersburg, Md. But when she stood up and took a
step, her holiday took a turn for the worse. Wallace fell and fractured
her hip.

"My foot dragged a little, not exactly a stumble," Wallace says. "I
don't know whether the bone broke because I fell, or I fell because the
bone broke."

                                 <Picture: [x-ray showing artificial
                                 left hip contrasted with bones of normal
                                 right hip]>

Despite her 84 years and weak heart, Wallace had a lot going for her
after her fall: modern medical practice and determination to walk again.
Surgery to implant an artificial hip joint took under 45 minutes. (The
x-ray at right shows the artificial left hip in sharp contrast with the
bones of the normal right hip.) Spinal anesthesia and sedation were
administered instead of general anesthesia because they are thought to
pose less risk. And her physical therapy began the day after the
operation.

"I fussed," she says. "I was afraid it was going to hurt or I'd fall.
But they said if you want to go home, you have to do this. And I did. It
was more scary than painful."

Wallace's fracture was one of 1.5 million--including 336,000 hip
fractures--reported in 1993, the latest year for which the National
Center for Health Statistics has figures.

Besides surgical repair, treatments for broken bones include bone
manipulation to reduce the fracture, use of a cast, and bone
stimulation. Central to fracture healing is bone biology. Many
treatments, some on the horizon, are designed to improve the natural
course of healing.

Bones at Work 

For skeletal growth and maintenance, the body's 206 dynamic, living
bones renew themselves lifelong through a continual breakdown, build-up
process known as remodeling. This process is also involved in the
remodeling of fractures, says Martin Yahiro, M.D., a Baltimore
orthopedist in private practice and a consultant on fracture treatment
devices to the Food and Drug Administration's Center for Devices and
Radiological Health.

In remodeling, complex chemical signals prompt cells called osteoclasts
to break down and remove (resorb) old bone, and others called
osteoblasts to deposit new bone. Many elements influence remodeling.
Among them: weight-bearing, vitamin D, growth factors, prostaglandins,
and various hormones, including estrogen, thyroid, parathyroid, and
calcitonin.

As 80 percent of the mature skeleton, compact cortical bone supports the
body, providing extra thickness mid-shaft in long bones to prevent their
bending. Cancellous bone, whose porous structure with small cavities
resembles a sponge, predominates in the pelvis and the 33 vertebrae from
the neck to the tailbone. A fibrous membrane called the periosteum
covers bone. 

For healing and health, living bone must have a steady supply of
nutrients. Blood vessels permeate bone to provide this lifeline.
Blood-forming elements fill the long bone inner canals.

When a Bone Breaks 

Fracture breaks continuity of bone and of important attached soft
tissue--including blood vessels, which spill their contents into
surrounding tissue.

Even before treatment, the body automatically seeks to repair the
injury. Inflammatory cells rush to destroy, dilute or isolate invaders
and injured tissue. Tiny new blood vessels called capillaries begin
growing into the site. Cells proliferate. The injured person usually
must endure pain, swelling, and increased heat at the breakage site for
one to three days.

New tissue bonds the fractured bone ends with a soft callus, a mass of
connective tissue and exudate (matter escaped through blood vessel
walls). Remodeling begins. Within a few months, a hard callus replaces
the soft one. Remodeling restores the inner canal.

Once restoration is complete, which may take years, the healed area is
brand new, without a scar. Usually thicker, the new bone may even be
stronger than the old, Yahiro says, adding that if the bone should break
again, it's unlikely to be at the same place.

And children's bones have a healing boost: They're growing.

"The growing skeleton is just geared to make bone," Yahiro says. "A very
young child's wrist bones grow a millimeter a month, to rapidly correct
misalignment or length defects. An adult may take six to eight weeks to
heal a wrist fracture, a 5-year-old only three."

When the ends of a fractured bone, such as an arm bone, form an abnormal
angle, the doctor must decide whether to push the ends together
(manipulation) to reduce the fracture, possibly under anesthesia. Simple
x-rays aid evaluation.

"If it's a large angle, we'd want to reduce that fracture," Yahiro says.
"But if it's a small angle, especially in a young child whose growth
will correct it, we'd probably just put the limb in a cast."

[The 95K JPEG graphic in the original text illustrates common sites of
bone fractures in seniors and younger people. (Source: National Center
for Health Statistics' National Hospital Discharge Survey, 1992.
Infographic by Sam Ward.)]

<Picture: [graph showing most common sites of bone fractures]>

Surgery for Joint Fractures 

Joint fractures usually require surgery, Yahiro says. "We try to restore
the joint to perfect, like putting a jigsaw puzzle back together."

An artificial joint can be used to replace a fractured head of the long
bone in the hip, like Wallace had, or in the shoulder.

Total hip joint replacements are mainly made of titanium or
cobalt-chrome alloys or other metals. Each replacement has a stem that
goes into the thigh bone inner canal, a ball for the head, and a plastic
cup socket--the latter usually only used if the joint is badly
arthritic. Yahiro often uses bipolar joints--a big ball atop a smaller
one. All these joint replacements are approved by FDA.

Approved replacements for fractures in shoulder joints also consist of a
ball and stem.

Andrew Bender, M.D., the orthopedist who implanted Wallace's partial
replacement, says this simple model has been in use 30 to 40 years. "It
has different size balls, one size stem, so it's not an exact fit. But
it gives what we call a three-point fixation for some immediate
tightness. The stem has holes for bone to grow through and across for
more permanence."

Bender pressed in Wallace's device without cement, a snug fit. He
cements only if the fit is very, very loose. "Modern day hip replacement
without cement is relatively quick, both sides. She had only one side
done and good bone, so it didn't take long."

If a replacement fails, it usually does so within 5 to 10 years. Simple
models tend not to fail in the very old, Yahiro says. "A person in a
chair or bed most of the time won't put demands on the joint that, say,
Bo Jackson does." (Jackson had a hip replacement in 1992 due to a
football injury.)

For higher demand, there are more precisely fitted models.

A robot that drills a more precise hole for the stem, to possibly keep
the joint intact longer, is under investigation for use in cementless
hip joint replacements. (See "Robots in the Operating Room," July-August
1993 FDA Consumer.)

An external fixator--a pin-and-rod frame--can keep the joint from being
compressed by other bones, to heal before a load, or stress, is put on
it again. Pins are inserted on one side of the limb through the skin,
muscle and bone, out the other side, and attached to the external rod,
forming the frame.

About 30 percent of patients get infected at the pin site, so meticulous
hygiene is crucial. "It's a race," says Kenneth McDermott, who reviews
the devices for the Center for Devices and Radiological Health. "The pin
goes through the skin, and infection can go right down the pin."

Internal fixation devices pose less risk of infection. These metal
plates, rods, wires, screws, nails, pins, staples, and anchors may
sometimes be left in. A tiny pin may not be felt, but plates or screws
may cause irritation or pain. The decision whether to remove the device
in a second surgery is made on a case-by-case basis.

Surgery to remove a screw in the very old may be too risky. For a
20-year-old, benefits of a second surgery may outweigh risks. In the
ankle, plates and screws are customarily removed. Yahiro says, "The
bones are so superficial, the device often rubs on the shoe."

McDermott gives another reason for removing a plate or screw: "It can
take the load off the bone, causing the bone to resorb and weaken."

Fixators and internal fixation devices are used also for some mid-bone
fractures.

Grafts 

The surgeon may graft bone to replace a missing segment that had to be
surgically removed due to infection.

For a small segment, tissue can be taken from the patient's own bone
(autologous graft).

Cadaver bone (allograft) may be used, especially for a large segment.
Though dead tissue, cadaver bone provides a scaffold for living bone to
grow into and remodel the graft. For healing to occur--and sometimes it
doesn't--the body must put blood vessels into the graft to nurture the
new living bone as it replaces the dead tissue. Healing takes longer
than with an autologous graft.

Another option is a substitute bone graft, fashioned with help from
nonhuman substances. FDA recently approved two such grafts:


 * Pro Osteon Implant 500 Coralline Hydroxyapatite Bone Void
   Filler(1992)--Fills holes near the ends of long bones in adults. It
   derives from marine coral, whose spongy calcium structure resembles
   human cancellous bone.

 * Collagraft Bone Graft Matrix(1993)--Treats long-bone fractures and
   other injury-caused areas of missing bone of 30 milliliters (1.8
   cubic inches) or less. The product--consisting of purified cow
   collagen and a chemical, hydroxyapatite-tricalcium phosphate--is
   mixed with the patient's marrow into a paste and put into the area of
   missing bone to encourage new bone growth. It's not for use in
   certain patients, such as those with osteomyelitis (bone
   inflammation) at the fracture site, severe allergies, or allergy to
   cow collagen, and those being desensitized to meat products, as the
   treatment injections may contain cow collagen.

When these substitute grafts are placed next to healthy bone, the body
remodels them in the same way it remodels human grafts. But according to
Center for Devices and Radiological Health reviewer Nadine Rosile, "The
substitute grafts aren't strong enough for use without a fixation device
to stabilize the fracture."

A bone filler paste now under investigation, however, is as strong as
bone within 12 hours, according to a report of a study of patients whose
wrist fractures were injected with the paste. The report, in the March
24, 1995, issue of Science, stated that the paste stabilized the bone
during healing and was eventually remodeled. The patients had greater
grip strength at six months than historical controls (other patients in
the past who had not been treated with the paste) had at two years, the
report stated.

Also under investigation are injections of growth factor proteins, such
as morphogenic protein and transforming growth factor-beta, found
naturally in the body in very small amounts.

"The proteins turn on cells to produce bone," Yahiro says. "Animal
studies show growth with injections similar to that with autologous
grafts." The hope, he says, is that injected fractures, even with large
areas of missing bone, will heal faster and be stronger, without grafts.

Healing Helpers 

FDA has approved seven electrical bone growth stimulators, mainly for
fractures at the middle of long bones, such as the shinbone (tibia),
that have not healed over at least nine months. Although exactly how the
stimulators heal is unknown, manufacturers' studies showed the devices
did in fact affect cellular processes.

Yahiro explains that loading (stressing) a bone produces in it a small
electrical field called piezo electric force, believed to stimulate new
bone formation. "It's believed that electrical stimulation does
something like that on a large scale," he says.

For direct stimulation, an electrode is implanted at the fracture,
linked through the skin to a generator. For indirect stimulation,
electric coils outside the limb on the non-fracture side induce an
electrical field at the fracture side.

In 1994, FDA approved the first ultrasound bone growth stimulator. The
Sonic Accelerated Fracture Healing System (SAFHS) is for adults with
small fractures in the lower leg or lower forearm. A cast or splint is
used. It is the first stimulator for the treatment of fractures
occurring within seven days before treatment. Studies suggest that
mechanical forces of the ultrasound waves transform into electrical
impulses as they travel through the tissues.

The SAFHS consists of a portable generator cabled to a small, square
treatment module that emits ultrasound pulses at about the same low
intensity as sonogram fetal monitors. In some instances, the patient may
use the unit at home. Recommended treatment is 20 minutes once a day
until the fracture heals.

The SAFHS is not for patients who need additional fixation or surgery,
are pregnant or breast-feeding, have bone disease or circulatory
problems, or take medicines that may adversely affect remodeling.

In studies, all treated patients--and especially older people--healed
faster than those using a placebo. In those age 50 and older, arms
healed 40 days faster, and legs 85 days faster. Six years' follow-up did
not suggest long-term adverse effects.

Stimulation, grafts, manipulation, joint replacements, casts. Whatever
the treatment, fracture healing is monitored by x-rays and physical
examination to answer such questions as: Does it hurt or move when
pushed on? On x-ray, does the fracture look healed? On x-ray, are the
bones aligned?

For Wallace, healing is now complete. She is indeed walking again, using
a cane as she did before the replacement surgery.

"If I don't use the cane, my leg aches," she says. "I'm still careful to
use my good leg stepping up a curb, and my bad leg stepping down, like I
learned in therapy."

Dixie Farley is a staff writer for FDA Consumer.


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


Boning Up

The most important influences on fracture healing are nutrition and
overall health, including bone health, before the injury, says
orthopedist Martin Yahiro, M.D., a consultant to FDA. "That's why it's
so important all your life to do weight-bearing exercise such as walking
and get enough calcium and vitamin D, so you lay down as much bone as
possible during growth and keep as much as you can later on."

The Recommended Dietary Allowance (RDA) for calcium is 1,200 milligrams
a day for people ages 11 to 24 and for pregnant or breast-feeding women.
For men and women older than 25 who no longer have to meet the greater
demands of growth, the calcium RDA is 800 milligrams a day.

In general, genes decide bone shape and size. But mechanical stress by
muscle, body weight, and physical activity influence bone shape and
density--and health--throughout life.

Simply put, loaded (stressed) bone strengthens, and unloaded bone
weakens. As examples, astronauts' bones weaken in outer space with no
gravity pull on them, and the shaft of the humerus (long upper arm bone)
in a professional tennis player's dominant arm gets denser and thicker
from the extra load.

The body increases its bone mass until, usually, the mid-30s, after
which a gradual loss begins.

Age-related bone loss can lead to osteoporosis, a condition of thin,
weakened bone that fractures easily. The condition affects many
postmenopausal women, because bone loss increases with menopause due to
lower estrogen levels.

In announcing its recent approval of Fosamax and Miacalcin Nasal Spray
for osteoporosis, FDA advised that patients also exercise and get
adequate calcium and vitamin D. Drugs approved by FDA to prevent or
treat osteoporosis are:

 * estrogen--Premarin, Ogen, and Estrace tablets; Estraderm patch

 * estrogen packaged with progestin hormone tablets--Prempro; Premphase

 * alendronate--Fosamax

 * calcitonin--Miacalcin Nasal Spray, Calcimar Injection, Miacalcin
   Injection, and Cibacalcin for injection.

--D.F.

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

Book Reopened on Infectious Diseases

by Margie Patlak 

In the late 1960s, after seeing such deadly diseases as smallpox, polio,
and rheumatic fever get tamed by vaccines or antibiotics, Surgeon
General William H. Stewart declared that it was time to close the book
on infectious diseases and pay more attention to chronic ailments such
as cancer and heart disease. 

This commonly held belief that the war on infectious diseases could be
won has been shattered by a score of new or reemerging diseases that
have surfaced in epidemics scattered across the globe over the last 15
years, with some occurring within just the last year or two.

The new epidemics, combined with a deeper understanding of disease
dynamics and the tricks microbes have up their sleeves, have shaken the
medical community and led to a less rosy outlook. An article in the Jan.
17, 1996, issue of the Journal of the American Medical Association
reported that infectious disease is now the third leading cause of
death, after heart disease and cancer. Deaths from infectious disease
rose 58 percent between 1980 and 1992, according to the article by
Robert W. Pinner, M.D., of the national Centers for Disease Control and
Prevention, and colleagues. Most of the increase is from AIDS cases. Yet
even without AIDS cases, the death rate from infectious diseases rose 22
percent.

Some infectious disease experts wager future epidemics will take a
greater toll on human life than those in the past, despite medical
advances made over the past century. We are increasingly more vulnerable
to infectious diseases, these experts point out, because of the growing
proportion of people residing in urban areas, which act as magnets for
epidemics. In 1800, less than 2 percent of the world's population lived
in urban communities. By the year 2000, however, that fraction is
expected to rise to 50 percent, according to the National Academy of
Sciences.

Air travel, in addition, allows diseases to spread between cities on
opposite ends of the globe in a matter of hours.

Prominent on the list of new or reemerging diseases that have health
officials concerned are invasive strep infections, tuberculosis (TB),
hantavirus pulmonary syndrome, malaria, and dengue. The Food and Drug
Administration is responsible for insuring the safety and effectiveness
of the drugs and vaccines used to curb infectious diseases.

[The map in the original text (a 95K JPEG graphic) shows some of the
locations of new or reemerging infectious diseases and the year the
first recent cases appeared. (Source: Centers for Disease Control and
Prevention.)]

<Picture: [map showing recent appearances of infectious diseases]>

Deadly Strep 

Changes in the Streptococcus bacterium that give it more punch are
credited with causing recent outbreaks of "flesh-eating" strep and
streptococcal toxic shock syndrome (strep TSS). The latter disorder
killed puppeteer Jim Henson in 1990. 

Both these infections are caused by invasive strep--a type of
Streptococcus that more readily spreads in the body than the types that
cause strep throat. Studies by Dennis Stevens at the Veterans Affairs
Medical Center in Boise, Idaho, suggest invasive strep is armed with two
powerful toxins. In the body's furious attempt to rid itself of one of
the toxins, the immune system can foster the destruction of infected
muscle tissue or the sheath that covers the muscle (the flesh-eating
manifestation) or prompt the body to go into shock, which is often
fatal, or both. Damage also is wreaked by the other toxin, an enzyme
that destroys tissue by breaking down protein.

Invasive strep usually enters the body through minor injuries, such as
deep bruises, punctures, or chicken pox blisters. Only rarely is the
deadly form of strep acquired through person-to-person contact. People
with invasive strep usually don't complain of a sore throat, but rather
often have flu-like achiness and fatigue that is followed by a number of
symptoms, including pain in one region of the body, cough and difficulty
breathing, or painful skin that is red, hot and swollen and gradually
purples and forms blisters. This can be accompanied or followed by
confusion, low blood pressure, and coma.

The antibiotics penicillin, erythromycin and clindamycin are the drugs
of choice for treating invasive strep infections; the earlier treatment
is begun, the better the outcome. Surgical removal of infected tissue,
possibly including limb amputation, may be necessary. Researchers are
currently testing a vaccine for invasive strep.

CDC estimates that about 15,000 cases of invasive strep infections occur
each year in the United States, and studies by Stevens and others
suggest one out of three people with invasive strep die. The infection
can kill in less than a week.

Like most diseases, invasive strep is not new; China experienced an
epidemic of flesh-eating strep in 1924, and strep infections were a
major cause of death in Chicago and other cities in this country in the
middle of the 19th century. It's not known for certain whether invasive
strep currently is on the rise in this country. At this point, however,
it is still considered a rare disease.

Tuberculosis 

After a comforting steady decline since the 1950s, TB incidence in the
United States began to climb in 1985, setting off alarms in the medical
community. According to CDC, in 1994 there were 24,361 cases of TB in
the United States--about 2,000 more cases than in 1984.

TB's comeback in this country is tied to the rising numbers of people
whose immune systems are weakened by HIV infection, cancer and
chemotherapy, or the drugs taken following an organ transplant. A
resurgence of the disease is also being fostered by increasing poverty
and drug abuse, as well as by increasing numbers of immigrants to this
country with TB. 

Well-known to the ancient Egyptians, TB is caused by airborne bacteria
expelled from the lungs when a person with active TB coughs, sneezes or
speaks. Repeated exposure to these droplets can infect another person's
lungs.

The immune defenses of healthy people usually prevent TB infection from
spreading beyond a small area of the lungs by creating a barricade
around the bacteria. This walled-up infection is called latent TB and
may be present throughout a person's life. People with latent TB test
positive on the TB skin test. About 10 to 15 million people in this
country have latent TB.

If the body's immune system is impaired, the TB bacteria may begin to
spread more widely in the lungs or to other tissues causing active TB
infection.

The early symptoms of active TB include fatigue, weight loss, fever,
chills, and night sweats. Once the infection has progressed, people may
develop a cough or chest pain, or produce sputum that may contain blood.
TB can spread beyond the lungs causing additional symptoms such as back
pain or blood in the urine.

FDA recently approved a sputum test for TB that gives results in four to
five hours, compared to the one to eight weeks required by conventional
sputum culture tests. The Amplified Mycobacterium TB Direct Test is for
use on specimens already shown likely to be positive for TB on an acid
fast stain test. The new test allows treatment to begin sooner, but a
follow-up conventional culture test must also be done.

TB is treated with a combination of several antibiotics, which have to
be taken for six to nine months to be effective. CDC recommends that
people with latent TB who develop HIV infection or another condition
that suppresses the immune system receive preventive therapy with the
antibiotic isoniazid, marketed under the brand name INH. People who have
been in close contact with someone with active TB and test positive on a
TB skin test should also take isoniazid, which is highly effective in
preventing a latent TB infection from progressing to active disease.

Drug-resistant strains of TB develop when people stop taking their TB
drugs too soon or take them incorrectly. About 90 percent of people with
TB that responds to standard antibiotics are cured of the disease. But
only 10 percent of those people afflicted with drug-resistant TB
survive. 

There has been a disconcerting increase in the number of drug-resistant
TB cases in outbreaks scattered across the country. (See "The Rise of
Antibiotic Resistant Infections" in the September 1995 issue of FDA
Consumer.) Particularly disturbing are the 1 out of 10 cases of
drug-resistant TB that have occurred in healthy people with normal
immune systems. They died at the same rate as those with faulty immune
systems afflicted with the drug-resistant TB. 

Noting the ease with which TB is passed from person to person, a 1992
National Academy of Sciences report on emerging infections warned that
drug-resistant TB "represents a major threat to health in the United
States." 

In response to the drug-resistance problem, FDA has pledged to speed up
the review process for new TB drugs. One TB drug is currently being
tested in a clinical trial, and another may soon undergo such testing. 

A vaccine that can prevent TB from spreading beyond the lungs is
available. But because the vaccine cannot reliably prevent TB lung
infections in adults, it currently is not recommended for general use or
for health-care workers, according to CDC. The vaccine is also
problematic because it causes people to test positive for a TB skin
test, which is the mainstay for TB surveillance in this country.

Hantavirus

The 1993 outbreak of hantavirus pulmonary syndrome (HPS) in the
Southwest caught health officials by surprise. The new syndrome
initially causes flu-like symptoms, and then causes its victims to gasp
for air as their lungs fill with fluid. The disease kills about half the
people it infects, usually within a week. There is no treatment approved
specifically for hantavirus, but researchers are currently assessing the
effectiveness of the antiviral drug Virazole (ribavirin) for HPS. A
vaccine is being developed.

HPS is caused by a hantavirus named Muerto Canyon (Valley of Death)
virus for the spot in New Mexico where it was isolated. It is carried by
rodents and passed to people who inhale the aerosol particles emitted by
the infected rodents' saliva, urine or feces. People can become infected
with hantavirus after being bitten by rodents. Many people who have
developed HPS live in mice-infested homes. One woman who developed the
disorder, however, was exposed to rodents her pet cat dragged into her
house. Another person succumbed to the disease after cleaning a
rodent-infested barn. Hantaviruses are not passed directly from person
to person.

Experts suspect that rodents in the western United States have harbored
the Muerto Canyon virus for quite some time, but unusual weather
conditions led to an explosion of the deer mouse population in the early
months of 1993. The boosted mouse population apparently triggered the
HPS epidemic by increasing contact between people and mice infected with
the virus.

Since first described in the spring of 1993, more than 100 cases of HPS
have been identified in 23 states, predominantly in the Western half of
the country, according to CDC. The rodents that can carry the Muerto
Canyon virus, however, live nearly everywhere in the United States.

The deer mouse population started declining shortly after the first HPS
cases were reported. Between early 1994 and mid-1995, only 37 cases of
HPS were reported to CDC, suggesting the hantavirus epidemic is waning. 

People can stem their risk of a hantavirus infection by ensuring their
homes and workplaces are free from rodents.

Airport Malaria

International jet-setting has fostered recent outbreaks of malaria in
the United States. Malaria is such a common import to countries that the
term "airport malaria" was coined to describe the outbreaks of the
disease that have occurred among travelers. About 1,000 cases of malaria
are imported into this country each year, according to CDC.

Malaria causes flu-like symptoms, and in severe cases can cause coma,
severe anemia, kidney failure, difficulty breathing, or death. The
disease is passed from person to person by mosquitoes that harbor the
malaria-causing parasites.

Malaria was a major problem in this country during George Washington's
time and, until the 1930s, was a major killer in the southern states.
The disease was virtually eradicated from the United States by 1955,
following a major campaign in which mosquito-infested areas were sprayed
with the pesticide DDT and swamps were drained or filled with oil that
killed mosquito larvae. People were also encouraged to screen the
windows of their homes.

Similar efforts worldwide shrank malaria's territory, but only
temporarily as mosquito-control efforts abated, mainly due to a lack of
funds, and mosquitoes resistant to the effects of pesticides increased.
According to the National Institute of Allergy and Infectious Diseases,
each year malaria now infects 300 million to 500 million people globally
and kills as many as 3 million.

There's concern that malaria might once again take root in the United
States because most states harbor mosquitoes that can carry malaria
parasites. Particularly disturbing are the recent small outbreaks of
malaria in California, Florida, Texas, New Jersey, and New York City.
Most of these cases were probably spread by infected immigrants or
migrant workers via local mosquitoes, according to CDC.

"The reintroduction of significant malaria into this country is ... very
possible," said Philip Coyne, M.D., medical officer in FDA's division of
anti-infective drug products.

Malaria can often be effectively treated with quinine or related
compounds. Drug-resistant strains of malaria parasites are posing a
problem worldwide, however, and raising the need for new antimalarial
drugs. FDA approved Halfan (halofantrine) in 1992. Its developer,
SmithKline Beecham, Inc., has chosen not to market it in the United
States. Some strains of malaria are already resistant to it. Other
antimalarial drugs and vaccines are currently being tested.

Break-Heart Fever

Another mosquito-spread illness on the rise worldwide and likely to make
a comeback in this country is dengue, which an 18th century Philadelphia
doctor called "break-heart fever" because of the depression that often
ensues following the illness. Dengue, which is caused by a virus, is
characterized by a sudden onset of high fever accompanied by severe
headache and muscle, joint and eye pain. A red rash can also develop all
over the body. The rash may be accompanied by itching and scaling.

A severe form of dengue, known as dengue hemorrhagic fever, causes
bleeding from the mouth, nose and vagina. Gastrointestinal bleeding and
numerous bruises also often occur. Such bleeding can trigger a loss of
blood pressure that can cause the body to go into shock. As many as 1
out of every 10 people who develop dengue hemorrhagic fever dies. There
is no treatment for dengue and dengue hemorrhagic fever, although
vaccines for the disorders are currently being developed.

Over the last 15 years, as mosquito control programs abated, dengue has
spread like wildfire. In the 1980s, major outbreaks spread throughout
Latin America, including Mexico, and the incidence of dengue hemorrhagic
fever skyrocketed.

The United States hasn't had any major epidemics of dengue since the
1940s. But there are travelers to this country who come down with the
disease each year, and a small number of people have developed dengue
from local mosquitoes in Texas. Both species of mosquitoes that carry
the dengue virus are firmly established in several southeastern states.

People traveling to dengue- and malaria-infested areas should use
DEET-containing insect repellent and stay in lodgings with screened
windows and mosquito nets for sleeping. Preventive drug therapy for
malaria is also advised. Travelers should consult with their physicians
about such treatment before leaving the country.

Other Health Threats

Other possible resurgent and emerging diseases include a dangerous kind
of E. coli infection spread by contaminated meat, drug-resistant
cholera, deadly Ebola infection, and a new disease called human
granulocytic ehrlichiosis, which is spread by the type of ticks that can
also carry Lyme disease. 

Experts can't predict if any of these diseases will become a great
problem. The best protection is to be aware of the possibility and take
precautions to prevent their spread. As a 1992 National Academy of
Sciences report on emerging infections points out, "despite a great deal
of progress in detecting, preventing, and treating infectious diseases,
we are a long way from eliminating the human health threats posed by ...
a broad array of microbes."

Margie Patlak is a writer in Elkins Park, Pa. 


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


Worldwide Prevention Efforts

"Prevention is so much better than healing because it saves the labor of
being sick," said Thomas Adams, a 17th century English preacher. Experts
convened by the National Academy of Sciences suggest:


 * Surveillance--to keep an extensive global lookout for new or
   reemerging infections so the health community can develop the
   appropriate containment measures before diseases spread to
   plague-like proportions.

 * Research--to help understand the factors that foster emergence of
   infectious diseases, and to develop better surveillance, diagnosis,
   treatment, and prevention tactics.

 * Vector control--to limit the spread of diseases transmitted by such
   vectors as insects and rodents by eradicating them.

 * Public education and behavioral change--To prevent spread of diseases
   through travel, poor personal hygiene, improper food handling, drug
   abuse, and high-risk sexual behavior.

--M.P. 

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

On the Teen Scene:
An Itch Like No Other

by Judith Levine Willis 

It's an itchy feeling you might hardly notice at first.

Maybe, you muse, it's just that your jeans are too tight.

Actually, tight jeans may have something to do with it. But if the itch
keeps getting itchier, even when your jeans have been off for awhile,
then there's something else involved.

That something else could very well be a fungus whose technical name is
Candida, and which causes what is often called a "yeast" infection. Such
infections are most common in teenage girls and women aged 16 to 35,
although they can occur in girls as young as 10 or 11 and in older women
(and less often, in men and boys as well). You do not have to be
sexually active to get a yeast infection.

The Food and Drug Administration now allows medicines that used to be
prescription-only to be sold without a prescription to treat vaginal
yeast infections that keep coming back. But before you run out and buy
one, if you've never been treated for a yeast infection you should see a
doctor. Your doctor may advise you to use one of the over-the-counter
products or may prescribe a drug called Diflucan (fluconazole). FDA
recently approved the drug, a tablet taken by mouth, for clearing up
yeast infections with just one dose.

Though itchiness is a main symptom of yeast infections, if you've never
had one before, it's hard to be sure just what's causing your
discomfort. After a doctor makes a diagnosis of vaginal yeast infection,
if you should have one again, you can more easily recognize the symptoms
that make it different from similar problems. If you have any doubts,
though, you should contact your doctor. 

In addition to intense itching, another symptom of a vaginal yeast
infection is a white curdy or thick discharge that is mostly odorless.
Although some women have discharges midway between their menstrual
periods, these are usually not yeast infections, especially if there's
no itching.

Other symptoms of a vaginal yeast infection include:

 * soreness
 * rash on outer lips of the vagina
 * burning, especially during urination.

It's important to remember that not all girls and women experience all
these symptoms, and if intense itching is not present it's probably
something else.

Candida is a fungus often present in the human body. It only causes
problems when there's too much of it. Then infections can occur not only
in the vagina but in other parts of the body as well--and in both sexes.
Though there are four different types of Candida that can cause these
infections, nearly 80 percent are caused by a variety called Candida
albicans.

Many Causes 

The biggest cause of Candida infections is lowered immunity. This can
happen when you get run down from doing too much and not getting enough
rest. Or it can happen as a result of illness.

Though not usual, repeated yeast infections, especially if they don't
clear up with proper treatment, may sometimes be the first sign that a
woman is infected with HIV, the virus that causes AIDS.

FDA requires that over-the-counter (OTC) products to treat yeast
infections carry the following warning:

"If you experience vaginal yeast infections frequently (they recur
within a two-month period) or if you have vaginal yeast infections that
do not clear up easily with proper treatment, you should see your doctor
promptly to determine the cause and receive proper medical care."

Repeated yeast infections can also be caused by other, less serious,
illnesses or physical and mental stress. Other causes include:

 * use of antibiotics and some other medications, including birth
   control pills

 * significant change in the diet

 * poor nutrition

 * diabetes

 * pregnancy.

Some women get mild yeast infections towards the end of their menstrual
periods, possibly in response to the body's hormonal changes. These mild
infections sometimes go away without treatment as the menstrual cycle
progresses. Pregnant women are also more prone to develop yeast
infections.

Sometimes hot, humid weather can make it easier for yeast infections to
develop. And wearing layers of clothing in the winter that make you too
warm indoors can also increase the likelihood of infection.

"Candida infections are not usually thought of as sexually transmitted
diseases," says Renata Albrecht, M.D., of FDA's division of
anti-infective drug products. But, she adds, they can be transmitted
during sex.

The best way not to have to worry about getting yeast infections this
way is not to have sex. But if you do have sex, using a condom will help
prevent transmission of yeast infections, just as it helps prevent
transmission of more commonly sexually transmitted diseases, including
HIV infection, and helps prevent pregnancy. Teens should always use a
latex condom if they have sex, even if they are also using other forms
of birth control. (See "On the Teen Scene: Preventing STDs" in the June
1993 FDA Consumer.)

If one partner has a yeast infection, the other partner should also be
treated for it. A man is less likely than a woman to be aware of having
a yeast infection because he may not have any symptoms. When symptoms do
occur, they may include a moist, white, scaling rash on the penis, and
itchiness or redness under the foreskin. As with females, lowered
immunity, rather than sexual transmission, is the most frequent cause of
genital yeast infections in males.

OTC Products 

The OTC products for vaginal yeast infections have one of three active
ingredients: butoconazole nitrate (Femstat 3), clotrimazole
(Gyne-Lotrimin and others), or miconazole (Monistat 7 and others). These
drugs are in the same anti-fungal family and work in similar ways to
break down the cell wall of the Candida organism until it dissolves. FDA
approved the switch of Femstat 3 from prescription to OTC status last
December. The others have been available OTC for a few years.

When you visit the doctor the first time you have a yeast infection, you
can ask which product may be best for you and discuss the advantages of
the different forms the products come in: vaginal suppositories
(inserts) and creams with special applicators. Remember to read the
warnings on the product's labeling carefully and follow the directions. 

Symptoms usually improve within a few days, but it's important to
continue using the medication for the number of days directed, even if
you no longer have symptoms.

Contact your doctor if you have the following:

 * abdominal pain, fever, or a foul-smelling discharge
 * no improvement within three days
 * symptoms that recur within two months.

OTC products are only for vaginal yeast infections. They should not be
used by men or for yeast infections in other areas of the body, such as
the mouth or under the fingernails.

Candida infections in the mouth are often called "thrush." Symptoms
include creamy white patches that cover painful areas in the mouth,
throat, or on the tongue. Because other infections cause similar
symptoms, it's important to go to a doctor for an accurate diagnosis.

Wearing artificial fingernails increases the chance of getting yeast
infections under the natural fingernails. Fungal infections start in the
space between the artificial and natural nails, which become discolored.
Treatment for these types of infections--as well as those that occur in
other skin folds, such as underarms or between toes--require different
products, most of which are available only with a doctor's prescription.

Knowing the causes and symptoms of yeast infections can help you take
steps--such as giving those tight jeans a rest--to greatly reduce the
chances of getting an infection.

And, if sometimes prevention isn't enough, help is easily at hand from
your doctor and pharmacy.

Judith Levine Willis is editor of FDA Consumer.

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

How to Avoid Infection

Here are some steps young women can take to make vaginal yeast
infections less likely:


 * Wear loose, natural-fiber clothing and underwear with a cotton
   crotch.

 * Limit wearing of panty hose, tights, leggings, nylon underwear, and
   tight jeans.

 * Don't use deodorant tampons and feminine deodorant sprays, especially
   if you feel an infection beginning.

 * Dry off quickly and thoroughly after bathing and swimming--don't stay
   in a wet swimsuit for hours.

 * It's better not to have sex in your teens, but if you're sexually
   active, always use a latex condom.


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


Updates



New Bottled Water Standards

New FDA standards for bottled water take effect May 13.

The final regulation, published last November in the Federal Register,
sets standard definitions for different types of bottled waters,
including artesian, ground, mineral, purified, sparkling, spring,
sterile, and well water.

The regulation also requires mineral water to meet the bottled water
quality standards. It must come from a protected underground source and
contain at least 250 parts per million in total dissolved solids.
Mineral water had previously been exempt from standards that apply to
other bottled waters.

The regulation also requires that water bottled from municipal water
supplies must be clearly labeled as such, unless it is processed
sufficiently to be labeled as "distilled" or "purified" water. The
regulation also requires accurate labeling of bottled waters marketed
for infants.

Bottled water, like all other foods regulated by FDA, must be processed,
packaged, shipped, and stored in a safe and sanitary manner and be
truthfully and accurately labeled. Bottled water products must also meet
specific FDA quality standards for contaminants.

(See "Bottled Water: New Trends, New Rules," in the June 1993 FDA
Consumer.) 

Lung Protection for Babies

For the first time, infants at high risk for certain lung problems have
a product to help reduce the severity of respiratory syncytial virus
(RSV) disease, the most common cause of lower respiratory infections in
children.

The product, RespiGam (Respiratory Syncytial Virus Immune Globulin
Intravenous (Human)), was licensed by FDA last Jan. 19 for use in
high-risk infants under 2 years old with lung problems due to
prematurity or chronic bronchopulmonary dysplasia. (Chronic
bronchopulmonary dysplasia causes abnormal cell and tissue growth.) 

RespiGam is made from plasma taken from large numbers of normal, healthy
individuals, and contains a high concentration of protective antibodies
against RSV. These antibodies do not prevent RSV infections, but do help
protect children against the most serious consequences of the virus.

In the United States, more than 90,000 children are hospitalized and
4,500 die each year from RSV.

Treatment with RespiGam begins in November before the first outbreaks of
RSV normally occur. The treatment regimen involves an intravenous dose
once a month through March.

Clinical trials whose data supported the licensing of RespiGam included
the pivotal PREVENT trial, a randomized, placebo-controlled,
double-blind study. PREVENT involved 510 patients who either had chronic
bronchopulmonary dysplasia and were younger than 2, or were born
prematurely and younger than 6 months.

In the PREVENT trial, RespiGam reduced hospitalizations by 41 percent
and reduced hospital time by 53 percent. In addition, children required
fewer days of supplemental oxygen during their hospital stays.

Because infants with pulmonary disease may retain fluids, a small
percentage of infants in the trials needed new or extra diuretics after
receiving RespiGam.

As with any human immune globulin product, rare allergic reactions to
RespiGam are possible. In addition, a small risk exists for the
transmission of blood-borne viruses. However, the risk is low because
plasma donors are screened carefully, and the product is treated with a
procedure that inactivates most significant blood-borne viruses,
including the one that causes AIDS.

RespiGam is manufactured by Massachusetts Public Health Biologic
Laboratories of Boston, and will be distributed by MedImmune Inc., of
Gaithersburg, Md.



New Tracks Speed Device Reviews

<Picture: [picture of train showing approvals of medical device
applications]>

Study of Ritalin's Cancer-Causing Potential

An animal study of Ritalin (methylphenidate hydrochloride), a stimulant
widely prescribed for children with attention deficit hyperactivity
disorder (ADHD), has produced a "weak signal" that the drug may have the
potential to cause cancer, according to FDA, which has taken steps to
alert health professionals to the possible problem.

The agency has asked the drug's sponsor, Ciba Pharmaceuticals, to
include the study findings in the labeling for Ritalin, and to alert
prescribers by sending them a Dear Doctor letter. The company complied
in late January. FDA also plans to initiate additional follow-up
studies, including both animal tests and epidemiological studies in
humans using Ritalin.

The agency continues to regard Ritalin as a safe and effective drug, but
says the potential risk needs to be considered and further studied
because of the increasing and often long-term use of Ritalin in
children. In the last five years, there has been about a two- to
threefold increase in the use of the product.

The agency's actions are based on findings of a draft report by the
National Toxicology Program on cancer-causing potential of Ritalin in a
study in mice and a study in rats.

The study in rats revealed no cancer-causing activity. The findings in
mice included increased rates of noncancerous liver tumors and, in males
only, the occurrence of cancerous liver tumors.

FDA considers the studies' results a signal of a weak cancer-causing
potential because:

 * The positive findings were seen in one species of rodent (the mouse)
   and in only one organ--the liver--which is known to be particularly
   likely to develop tumors to a wide variety of stimuli.

 *The increased rates were seen primarily in nonmalignant tumors.

 *There was no increase in mortality associated with the tumors.

The agency also noted that animal studies do not necessarily reflect
human findings. The kind of liver tumor found in mice is extremely rare
in people, and its occurrence in recent years has not increased despite
the increased use of Ritalin. 

Clotting Factors and Hepatitis A

Hemophiliacs using Alphanate (Factor VIII) or AlphaNine S-D (Factor IX)
clotting factors for their bleeding disorders should check their supply
to make sure they don't use certain lots withdrawn from the market due
to an association with hepatitis A virus (HAV) infection, FDA has
advised. 

Alpha Therapeutics Corp., Los Angeles, withdrew Lot AP5014A Alphanate
last Dec. 8 due to suspected HAV transmission in three patients. Testing
showed the illness in two of them to be linked to the withdrawn lot.

Later, a fourth case of hepatitis A was reported after a patient had
received Alpha Therapeutics' AlphaNine S-D. Although HAV transmission by
the product is unproven, as a precaution pending further investigation,
the firm (with FDA's concurrence) placed on hold further distribution of
AlphaNine S-D Lots CA5410A, CA5412A, CA5413A, and CA5421A.

FDA last January also advised hemophiliacs using any human-derived
Factor VIII or Factor IX products to contact their doctors for hepatitis
evaluation if they have flu-like illness with jaundice or liver
tenderness. FDA advised doctors to report otherwise unexplained cases of
hepatitis A to their state health department pending further instruction
from the national Centers for Disease Control and Prevention.

HAV infection in children usually produces no symptoms. The infection is
most serious in older patients, in whom deaths infrequently occur. In
February 1995, FDA approved a vaccine that prevents HAV.

While reports of HAV transmission by clotting factor concentrates are
uncommon, laboratory studies and surveillance are under way to determine
whether transmission may occur from other products. 

Mammography Quality Improves

The quality and reliability of mammograms in the United States have
improved under FDA's new standards for taking and interpreting the
breast x-rays, according to a recent report from the General Accounting
Office (GAO).

FDA was given the responsibility of implementing the 1992 Mammography
Quality Standards Act passed by Congress in response to concerns that
women were dying as a result of poor mammography practices in many
facilities.

The GAO report, released Nov. 1, said that when the new rules went into
effect, about one-third of the clinics failed to meet the standards for
accreditation. On second attempts, about two-thirds of the clinics that
had earlier failed were able to pass, and still more passed on a third
attempt.

According to the report, only about 4 percent, or 400, of the 10,000 to
11,000 mammography facilities in the country stopped operating, and in
97 percent of those cases, another clinic was within 25 miles.

Breast cancer strikes 182,000 women a year and kills 46,000. Mammography
is currently the best method available to detect and treat breast cancer
early, when it is most curable.

The National Cancer Institute recommends that all women over 50 have
annual mammograms and that some women under 50 have them as well. 

1995 Dietary Guidelines Include New Weight, Exercise Advice

New weight recommendations and increased emphasis on exercise are
included in the advice offered in the recently issued 1995 edition of
the Dietary Guidelines for Americans.

Developed by the U.S. departments of Health and Human Services and
Agriculture, the 1995 Dietary Guidelines also reiterate the seven core
recommendations of past editions, once again emphasizing balance,
moderation and variety in food choices.

For the first time, the guidelines advise adults to maintain their
weight in a single healthy range rather than increasing it over the
years.

The new guidelines increase emphasis on physical activity, calling for
30 minutes or more of moderate physical activity on most (preferably
all) days of the week. Physical activities can include brisk walking,
calisthenics, home care, gardening, moderate sports exercise, and
dancing.

The guidelines also acknowledge for the first time vegetarian diets as a
healthful dietary alternative.

The Dietary Guidelines are published every five years. In addition to
providing information for consumers, they form the basis for federal
nutrition policy and programs.

A copy of the Dietary Guidelines bulletin may be obtained by:

 * sending your name, address and 50 cents to Consumer Information
   Center, Department 378-C, Pueblo, CO 81009

 * downloading from the USDA Center for Nutrition Policy and Promotion's
   home page at http://www.usda.gov/fcs/cnpp.html; or the Department of
   Health and Human Services home page at http://www.os.dhhs.gov/; or
   from USDA's Food and Consumer Service electronic bulletin board on
   FedWorld, modem number: (703) 321-3339.


New Reprint

A new FDA Consumer reprint is available free.

To order single copies of "A Status Report on Breast Implant Safety"
(FDA 96-4262), write to FDA, HFE-88, Rockville, MD 20857. To order 2 to
100 copies, write to FDA, HFI-40, at the same address, or fax your order
to (301) 443-9057. Include the publication number. 

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


Consumer Forum



Breastfeeding Article Excellent

The October issue of FDA Consumer includes a comprehensive article on
breastfeeding by Rebecca D. Williams, "Breastfeeding Best Bet for
Babies." I commend Ms. Williams for an excellent depiction of breastmilk
as a healthcare issue, an accurate explanation of the lactation process
and helpful tips for nursing parents. I hope future issues will provide
readers with updates on breastfeeding research and topical breastfeeding
issues.

The National Breastfeeding MediaWatch campaign, sponsored by the Texas
Department of Health, is an ongoing project of the Bureau of Nutrition
Services. Its purpose is to identify references to breast and formula
feeding in all facets of the media. Volunteers often write letters to
the various forms of media regarding the messages they send to the
public. A Fort Worth, Texas, participant shared Ms. Williams' article
with me.

If you would like more information about breastfeeding or the National
Breastfeeding MediaWatch campaign, please contact Ms. Laurie Coker,
Breastfeeding Promotion Specialist, at (512) 406-0744.

Jacquelyn McDonald, Director
Division of Nutrition, Education, Outreach, and Training
Bureau of Nutrition Services
Texas Department of Health

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


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.


Tobacco vending machines are no longer permitted in federal government
buildings, according to a General Services Administration final rule
effective last Jan. 25. The rule implements the "Prohibition of
Cigarette Sales to Minors in Federal Buildings and Land Act," which also
prohibits the distribution of free samples of tobacco products in space
owned and leased by the government. (FR Jan. 25)

Quality assurance program and inspection guidance is available in a
revised FDA compliance policy guide. "FDA Access to Results of Quality
Assurance Program Audits and Inspections" provides general policy and
guidance to FDA staff and may be useful to industry representatives. For
a free copy, send a self-addressed label to Tom Chin, Office of
Enforcement (HFC-230), Rockville, MD 20857; telephone (301) 827-0410.
(FR Jan. 24)

Human food safety and antimicrobial drug residues in food animals are
addressed in an FDA Center for Veterinary Medicine guidance document.
"Microbiological Testing of Antimicrobial Drug Residues in Food" gives
information about which antimicrobials may require supplemental testing,
and recommends tests for establishing that drug residues will not cause
intestinal problems in consumers. For a free copy, request Docket No.
93D-0398, and send two self-addressed labels to Communications and
Education Branch (HFV-12), Rockville, MD 20855. (FR Jan. 30)

Food animal use of fluoroquinolone antimicrobial drugs is the subject of
a report by FDA's Center for Veterinary Medicine. The report addresses
concerns that the drugs may increase development of
fluoroquinolone-resistant organisms that could be passed from animals to
humans and cause disease. For a free copy, request Docket No. 95S-0199,
and send two self-addressed labels to Communications and Education
Branch (HFV-12), Rockville, MD 20855. (FR Jan. 4)

Raw meat and poultry nutritional labeling and safe handling information
is available in a report from the U.S. Department of Agriculture's Food
Safety and Inspection Service. The report provides data from a survey on
food retailers' efforts to give consumers the information. For a free
copy of the report, request Docket No. 95-053N, and send a
self-addressed label to Charles R. Edwards, Product Assessment Division,
FSIS, U.S. Department of Agriculture, Washington, DC 20250. (FR Jan. 29)

Gaps in education may result in gaps in health care, according to a
report by the National Center for Health Statistics. "Health, United
States, 1994" shows that among people between 25 and 64, those with less
than a high school education had more than double the death rate as
those with at least one year of college. It also shows that women who do
not finish high school are nearly eight times as likely to smoke during
pregnancy as women who graduate college. Overall, the report states, the
percent of women who smoked during pregnancy dropped from 20 percent in
1989 to 17 percent in 1992. For a free copy of the report, write to NCHS
Data Dissemination Branch, Room 1064, Hyattsville, MD 20782; telephone
(301) 436-8500; internet http://www.cdc.gov/nchswww/nchshome.htm.
(Public Health Reports, September-October 1995)

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

Investigators' Reports



Illegal Use of Vet Drug Results in Fines, Probation

by Dixie Farley 

Investigation by FDA agents in Missouri and New York led last fall to
fines and probation for one man and deferred prosecution for another on
charges of prescription drug misbranding and product tampering.

On Sept. 8, 1995, the U.S. District Court for the Eastern District of
Missouri, St. Louis, fined Joseph Schilling, 31, of St. Louis, $1,000
with $25 special assessment, and sentenced him to three years' probation
with mandatory drug testing. Schilling had pleaded guilty to drug
misbranding caused by dispensing a prescription drug without a license.

On Oct. 17, 1995, the U.S. District Court for the Southern District of
New York, New York City, accepted Dean Gabriel, 25, of New York City,
into a six-months deferred prosecution program. Gabriel was charged with
product tampering.

Following a tip from an informant, St. Louis police began surveillance
of Schilling on Feb. 11, 1994, arresting him sometime after midnight on
suspicion of possessing a narcotic and marijuana. In Schilling's
apartment, the police seized drug paraphernalia and vials of suspected
Ketaset (ketamine), a veterinary anesthethic. Schilling cooperated with
the police and named Gabriel as his source.

Because FDA regulates Ketaset as a veterinary drug and the drug is not a
controlled substance regulated by the Drug Enforcement Administration,
the police notified the agency's Kansas City Office of Criminal
Investigations (OCI), which in turn notified OCI agents in the New York
field office, Jersey City, N.J. In deference to probable federal
charges, the local charges were held in abeyance.

Kansas City agents began investigating Schilling, and New York agents
investigated Gabriel with surveillance, examination of subpoenaed bank
and telephone records, and electronic monitoring.

The agents learned Schilling had met Gabriel in 1993 during a
Thanksgiving vacation in Miami. Schilling had some "Special K," the
street name for Ketaset, which they both used to get high.

Schilling told agents that after he and Gabriel returned home from
Miami, he asked Gabriel to supply him with more Special K, and that
Gabriel had done so twice. On March 28, at OCI's request, Schilling
ordered more Special K from Gabriel, receiving 30 vials, worth about
$1,350, on April 28.

Testing by FDA's Forensic Chemistry Center, in Cincinnati, determined
the substance in the vials was indeed ketamine.

In October, OCI agents asked the New York U.S. attorney to file a
complaint. Gabriel was arrested Nov. 16, 1994, on charges of tampering
with Ketaset by altering it so that it could be used illegally, thus
risking injury to another person.

On June 8, 1995, Schilling pleaded guilty to an information charging him
with misbranding a prescription veterinary drug in interstate commerce.

Gabriel's deferred prosecution program requires him to report to a
pretrial services officer, obey laws, associate only with law-abiding
individuals, and remain within the Southern and Eastern Districts of New
York or the District of New Jersey unless his supervising officer grants
him permission to leave. If Gabriel meets these conditions throughout
the six months, the government will not prosecute him.

Dixie Farley is a staff writer for FDA Consumer. 


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


Cheese Maker Says He Wants Out

An Ohio cheese manufacturer and distributor told the government he would
go out of business rather than comply with a court order to rid his
operations of dangerous bacteria and filth.

On July 12, 1995, Dominic Gangale, owner of Union Cheese Co.,
Sugarcreek, Ohio, told U.S. Magistrate Judge Patricia A. Hemann in the
U.S. District Court for the Northern District of Ohio that the firm had
ceased all cheese production, and he wanted only to sell the cheese in
stock.

The judge had ordered the firm on June 16 to stop making and
distributing cheese until it could ensure that the cheese was not
contaminated with pathogenic bacteria or filth.

In 1994, samples of cheese had tested positive for Listeria
monocytogenes, an organism that can cause serious and sometimes fatal
infections in small children, frail and elderly people, and others with
weakened immune systems. Although healthy individuals may suffer only
short-term symptoms, such as high fever, severe headaches, stiffness,
nausea, abdominal pain, and diarrhea, Listeria infection can cause
miscarriages and stillbirths in pregnant women.

Union Cheese produced about 20,000 pounds (9,072 kg) of Swiss cheese
daily and usually kept an inventory of about 1 million pounds (454,000
kilograms) of cheese, both its own Swiss, as well as different kinds
from other manufacturers.

On Sept. 29 and 30, 1994, Phillip Pontikos, an investigator with FDA's
Brunswick, Ohio, office, inspected Union Cheese as part of the agency's
scheduled surveillance of food manufacturers.

Pontikos found numerous violations of good manufacturing practices. In
one container of brine and cheese, he counted more than 30 floating dead
flies. He also saw dead insects on blocks of cheese and hundreds of dead
insects, cobwebs and dirt on windowsills.

He also noted that there was no hot running water in the restrooms,
brine room, or laboratory.

Pontikos discussed these problems with Annette Gangale, daughter of the
owner. She agreed to discuss the problems with her father.

Pontikos sent samples of cheese to FDA's lab in Cincinnati. One sample
tested positive for Listeria.

The agency advised the firm of the sample analysis, and as a result,
Union Cheese recalled cheese from the contaminated lot. But the recall
could not be completed because the company had not properly coded cheese
lots. Gangale admitted that he did not know exactly what firms had
bought the cheese.

On Oct. 27 and 28 and Nov. 7, Pontikos returned to Union Cheese and
collected more samples of cheese and environmental samples, including
brine and various materials from the floor. Several of the environmental
samples tested positive for Listeria.

On Nov. 29, Pontikos, along with FDA investigators Steve Kilker and
Frederick Lochner, returned to Union Cheese. In a two-week-long
investigation, they found many of the same problems Pontikos had seen
previously, as well as:

 * raw and finishing operations not being kept sufficiently separate

 * Swiss cheese being shipped before the end of the required 60-day
   aging period

 * ceiling condensation dripping onto uncovered cheese

 * peeling ceiling paint directly above the cutting table

 * cutting tools that could not be sanitized because of wooden handles
   and rusty screws.

On Feb. 22, 1995, the agency asked the Justice Department to initiate
injunction proceedings against Union Cheese. But, to confirm that the
problems still existed, the court ordered another inspection. When FDA
investigators returned to inspect the firm from May 16 to 18, many of
the same insanitary conditions still existed. One instance in which some
effort was made to improve things only made matters worse. A fan, placed
in the cutting room to prevent condensation from dripping on cheese,
drew air into the facility from the direction of the firm's sewage
treatment plant.

At a three-day hearing begun June 5, Gangale did not dispute the
investigators' findings. He said, however, that, in his opinion, these
problems did not violate good manufacturing practices.

At the end of the hearing, Judge Hemann ordered Union Cheese to close
until violations were corrected.

On July 12, the court entered a supplemental order clarifying the
conditions the defendants must comply with before they would be allowed
to sell cheese in stock. Those conditions called for FDA to supervise
the testing of each lot of cheese for Listeria and to ensure that the
cheese would be handled under sanitary conditions.

All the in-stock cheese--3,981 blocks, each weighing 200 pounds (90.7
kg)--tested free of Listeria, but one lot was insect-infested. All were
sold except for the insect-infested lot (72 blocks). At press time in
February, Gangale still had not destroyed the insect-infected lot.

--Dori Stehlin 


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


Animal Drug Maker Overhauls System

A major manufacturer of generic animal drugs chose to overhaul its
injectable drug processing system following a government seizure of
thousands of dollars worth of drugs, a partial factory shutdown, and a
consent decree in which the company agreed to correct violations.

At press time in February, Anthony Products Co., of Arcadia, Calif., was
planning to have its new injectables' operation at its El Monte, Calif.,
plant up and running this spring, pending FDA's concurrence, according
to Mary LoVetere, a compliance officer with FDA's Los Angeles district
office. The company already replaced its injectables' system at its
Irwindale, Calif., plant.

The company reportedly bought new equipment, hired new people, and
revised manufacturing procedures and controls so that its injectable
drug product line would comply with good manufacturing practices (GMPs),
she said.

Anthony Products makes various veterinary medicines, including
injectable forms of antibiotics, anesthetics and other drugs for large
and small animals. It manufactures drugs under its own brand name and
other companies' labels.

The company agreed to correct GMP violations in a consent decree it
signed Aug. 3, 1995, in the U.S. District Court for the Central District
of California.

In March 1995, U.S. marshals had seized, at FDA's request, about 200
drums of drug ingredients and 8,000 vials of injectable drugs. The
company's injectable drug system at its El Monte plant has been idle
since. Its penicillin production line at its Irwindale plant resumed
manufacturing in June 1995.

Previously, FDA sent Anthony Products several warning letters for
failing to follow GMPs for its injectable drugs. The most recent warning
was issued in May 1994, and company officials responded that they would
correct the violations.

However, during a reinspection in August and September 1994, FDA
investigators found continuing problems, as well as some new ones. The
problems revolved around the company's failure to ensure the sterility
and quality of its injectable products.

FDA decided to seek a seizure to spur the company to correct repeated
violations and to make sure that adulterated drugs did not reach
consumers.

On March 3, 1995, U.S. marshals seized all injectable drugs and
injectable drug ingredients in Anthony's possession.

In the consent decree, FDA agreed to return the raw ingredients to
Anthony Products for testing under GMPs. The seized drugs will be
disposed of by U.S. marshals.

--Paula Kurtzweil


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


Filth in Fish Fillets Closes Business

A food business closed after an FDA inspection found flies, condensate
dripping on smoked salmon fillets, racks of product placed against
fish-residue-encrusted walls, and fillets being trimmed with rusty
pliers.

FDA investigators found those and other unsanitary conditions at Sotra
Smoked Fish, U.S.A. Inc., Kingston, N.Y., after routine agency sampling
showed products contaminated with Listeria monocytogenes, bacteria that
can cause potentially fatal illness.

About 25 percent of such infections result in death, said FDA
microbiology expert Joseph Madden, Ph.D., in testimony concerning Sotra.
"Symptoms are most severe in the elderly, infants, pregnant women, and
those people whose immune systems are impaired," he said.

Sotra principal officers Olav Isaksen and Joel Kudlowitz signed a
consent decree of permanent injunction last June 23 in the U.S. District
Court for the Northern District of New York. Isaksen is president and
treasurer, and Kudlowitz is vice president and secretary. Sotra is
closed until it can meet the decree's terms, which include a cleanup and
an extensive testing program supervised by FDA's Buffalo district
office.

On June 1, 1994, investigator Thomas Morgan, of FDA's Boston district
office, sampled Sotra's fillets at a smokehouse in Bennington, Vt., as
part of the agency's seafood sampling program. Testing at FDA's
Winchester Engineering and Analytical Center, in Winchester, Mass.,
detected Listeria, and Boston informed the agency's Buffalo office.

Buffalo FDA investigator Margaret Slimbach visited Sotra July 7 to
present the test results.

Meanwhile, according to Buffalo compliance officer Raymond Kent, FDA
discussed Sotra with the New York State Department of Agriculture and
Markets, which inspects manufacturers for FDA under contract. In August
1993, the agency learned, the state had sent Sotra a warning letter and
levied a $300 fine because of continuing unsanitary conditions seen
during several state inspections in 1992 and 1993.

On July 12, Slimbach and Samuel Eskenazi, a microbiologist with FDA's
Northeast Regional Laboratory, began an extensive inspection of the food
plant. On the third day, Sotra agreed to recall the lot sampled in
Vermont.

The FDA team discovered gross unsanitary conditions and practices. The
freezer and cooler handles, for example, were slick with dirty residues.
And the cooler door had been left standing open about an hour and a
half, the inside temperature unmonitored. Using an FDA thermometer,
Slimbach found the temperature to be 60 degrees Fahrenheit (15 Celsius),
when it should have been below 40 F (4 C). (Listeria bacteria can grow
at 40 F, but not as fast as at higher temperatures.)

Other problems included:

 * inadequate use of hair coverings

 * no use of hand sanitizing solution

 * handling of fish with unwashed hands after returning from the
   restroom or other areas or after touching unsanitized equipment

 * routine placement of racks of fish against a cement wall encrusted
   with residues from previous operations

 * fish lying directly below the cooler's bottom panel, which was
   heavily coated with condensate droplets

 * use of rusty pliers for trimming products

 * uncleanable floors and walls due to pitting, cracks and peeling

 * residue-encrusted fillet rinsing hose touching the dirty floor

 * flies (known to transmit Listeria bacteria) in the production room

 * no tray to catch dead flies under the electric fly zapper.

Slimbach and Eskenazi collected swabs from numerous sites in the plant
for contaminant testing. At the end of the inspection, they informed
Sotra of the problems. Isaksen and Kudlowitz promised immediate
corrections.

FDA's Northeast Regional Laboratory's testing of the swabs showed
Listeria on such sites as the slicing and skinning machine blades,
condensate dripping onto salmon, stagnant water in the cooler, on cooler
and freezer door handles, on the wall, and under the fly zapper. The
bacterium was also identified in samples of finished salmon.

On Aug. 18, 1994, Slimbach returned to Sotra with a state investigator
to present these test results and see whether the firm had cleaned up.
It hadn't. The state seized all fish at the plant. Kudlowitz agreed to
recall the sampled lots and to destroy them and the seized product.

On Nov. 13, 1994, FDA asked the Department of Justice to file an
injunction against Sotra. In a letter two days later, FDA informed
Isaksen that the agency considered the recalled salmon to have posed a
life-threatening health hazard, and that Sotra must take appropriate
measures to prevent further contamination.

In signing the consent decree, Sotra agreed not to process, prepare,
pack, label, hold, or sell food in interstate commerce until it:

 * establishes methods, facilities and controls that ensure foods do not
   become contaminated with pathogenic bacteria or filth

 * provides certification to FDA by a qualified outside person that the
   sanitation control program is adequate

 * provides a written report to FDA detailing actions taken to ensure
   that foods are not contaminated or held under unsanitary conditions

 * has food tested by a qualified outside laboratory for Listeria, with
   results and analytical worksheets submitted to FDA

 * establishes a label review program, supervised by a qualified person,
   that ensures legal labeling

 * receives written notice from FDA that the requirements appear to be
   met.

FDA will closely monitor Sotra when it resumes operating. For example,
for three months, Sotra is to have an outside laboratory conduct
bacterial testing of finished and in-process products, food contact
surfaces, and other sites and report results to FDA. If bacteria are
found, testing is to continue as long as FDA specifies.

FDA is unaware of any complaints or illnesses related to Sotra products.

"We're still monitoring the second recall," FDA's Kent says.

--Dixie Farley

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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.


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SEIZURE ACTIONS

Food/Contamination, Spoilage, Insanitary Handling

PRODUCT: Lobster Tails, at Miami, Fla. (S.D.Fla.); Civil No. 95-0140.

CHARGED 1-25-95: While held for sale after shipment in interstate
commerce at Emerald Fisheries, Inc., in Miami, Fla., the articles were
adulterated in that they consisted of decomposed lobster
tails--402(a)(3).

DISPOSITION: A consent decree authorized the release of the goods for
reexportation to the original foreign vendor. (F.D.C. No. 67059; S. No.
95-735-458; S.J. No. 1)


PRODUCT: Mussels, canned in brine, at Los Angeles, Calif. (C.D.Calif.),
Civil No. 95-4878 DT.

CHARGED 7-24-95: While held for sale after shipment in interstate
commerce at G & K Sales in Los Angeles, Calif., the articles were
adulterated due to rancidity and texture breakdown--402(a)(3).

DISPOSITION: A default judgment ordered the articles destroyed. (F.D.C.
No. 67096; S. No. 95-713-949; S.J. No. 2)


PRODUCT: Shrimp, frozen, at Miami, Fla. (S.D.Fla.); Civil No. 94-1970.

CHARGED 9-21-94: While held for sale after shipment in interstate
commerce at Northwestern Meat, Inc., in Miami, Fla., the articles were
adulterated in that they contained insects, rodent hair, and cat or dog
hair--402(a)(3).

DISPOSITION: A default decree of condemnation ordered the articles
destroyed. (F.D.C. No. 66961; S. No. 94-595-108; S.J. No. 3)


PRODUCT: Shrimp, frozen, at Mobile, Ala. (S.D.Ala.); Civil No.
93-0530-CB-C.

CHARGED 6-23-93: While held for sale after shipment in interstate
commerce at Christian Salvesen Cold Storage in Mobile, Ala., the
articles were adulterated in that they consisted of decomposed
shrimp--402(a)(3).

DISPOSITION: A consent decree of condemnation and destruction ordered
the articles destroyed. (F.D.C. No. 66734; S. No. 93-575-037; S.J. No.
4)



CRIMINAL ACTIONS

DEFENDANT: Duramed Pharmaceutical, at Cincinnati, Ohio (D.Md.); Civil
No. HAR-30-0207.

CHARGED 5-24-93: Counts 1 and 3: The defendant introduced into
interstate commerce unapproved new drugs that were manufactured with
data generated on different product formulas from those requested on the
approved new drug application--301(d) and 303(a)(1). Count 2: The
defendant introduced into interstate commerce an adulterated drug. The
drug was adulterated in that the defendant made a material change in the
coating procedures of the product without obtaining approval from
FDA--301(a) and 303(a)(1). 

DISPOSITION: Guilty plea; entered into a consent decree of permanent
injunction and ordered to pay a $500,000 fine. (F.D.C. No. 66101; S.J.
No. 5)



INJUNCTION ACTIONS

DEFENDANTS: Kabi Pharmacia, Inc. and Anders Wiklund, at Piscataway, N.J.
(D.N.J.); Civil No. 93-3199 (JWB).

CHARGED 7-19-93: The defendants introduced into interstate commerce a
misbranded and unapproved new drug--301(a) and (d). The defendants also
caused the drug to be misbranded while held for sale after shipment in
interstate commerce--301(k).

DISPOSITION: A consent decree of permanent injunction was filed and
granted. (Inj. No. 1339; S.J. No. 6)



DEFENDANTS: Maple Island, Inc., Daniel W. O'Brien, and Ronald B. Zirbel,
at Wanamingo, Minn. (D.Minn.); Civil No. 4-93-789.

CHARGED 8-17-93: While held for sale at Maple Island, Inc., in
Wanamingo, Minn., infant and special nutritional dietary formulas were
adulterated in that they were manufactured, prepared, processed,
packaged, and held for sale under insanitary conditions whereby they
might have been contaminated with filth or rendered injurious to
health--402(a)(4). The articles were also adulterated in that they
contained Salmonella bacteria which might have rendered them injurious
to health--402(a)(1). Defendants caused the adulterated articles to be
introduced into interstate commerce--301(a). The defendants also
manufactured, processed, packaged, prepared, and held the articles for
sale after one or more of their components were shipped in interstate
commerce--301(k).

DISPOSITION: Several products were recalled and destroyed. Defendants
entered into a consent decree and resumed business upon compliance.
(Inj. No. 1332; S. No. 93-658-050; S.J. No. 7)



DEFENDANTS: Tuente Livestock, Ronald W. Tuente, and Roger B. Tuente, at
Yorkshire, Ohio (S.D. Ohio); Civil No. C-3-94-336.

CHARGED 8-15-94: The defendants caused adulterated swine to be
introduced into interstate commerce--301(a) and 512(a)(1). The swine
were adulterated in that they contained the presence of an unsafe new
animal drug--402(a)(2)(D).

DISPOSITION: The defendants entered into a consent decree in which they
agreed to surrender their livestock dealing licenses and to withdraw
from the livestock dealing trade for six years. (Inj. No. 1351; S. No.
94-708-236; S.J. No. 8)



MISCELLANEOUS ACTIONS

ACTION: Schering Corporation v. FDA, at Kenilworth, N.J. (D.N.J.); Civil
No. 93-3493 (HLS).

CHARGED 8-10-93: Plaintiff challenged a regulation implementing the
bioequivalence requirements for generic drugs under the abbreviated
application procedure. Plaintiff claimed the regulation impermissibly
broadened the statutory definition of bioequivalence.

DISPOSITION: The district court granted a summary judgment in favor of
FDA. The appellate court affirmed the district court's decision.
Plaintiff filed a petition for certiorari which was denied. (Misc. No.
1003; S.J. No. 9)


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Administration. Each issue contains in-depth feature articles written
for the general public on FDA-related health issues. The magazine also
includes reports from FDA's own investigators that go behind the scenes
to show how the agency protects the public from unsafe or worthless
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FDA Consumer is published monthly, except for combined issues for
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per year by writing:

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Washington, DC 20402-9371.

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