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

FDA Consumer magazine
(January-February 1997) VOL. 31 NO. 1


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


Features

New Ways to Prevent and Treat AIDS
Home-use blood collection kits, lab tests that don't require blood, and
new drugs are just a few of the new ways of diagnosing and treating HIV
infection.

Second Skins
Artificial skin and new types of wound dressings are among the advances
in treating burn patients and others whose skin has been seriously
damaged.


Overcoming Infertility
Distinguishing myth from medical fact is often the first step towards a
dearly desired, but elusive, pregnancy. Tests for men and women, drugs,
and surgery are some of the modern options that may help solve this
age-old problem.

Breast Reduction Often Good Medicine
Reducing the size of breasts considered overly large from a medical
standpoint often means also reducing head, neck and shoulder pain. Such
surgery can also make mammography easier and more accurate.


Treating Tropical Diseases
Americans traveling to certain areas of the globe may contract tropical
diseases despite their best efforts to avoid them. Fortunately,
effective treatments are available for most of these exotic maladies.


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


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.

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


New Ways to Prevent and Treat AIDS

by Mike Kubic 

Preventing and treating AIDS is one of the Food and Drug
Administration's top priorities. A new class of drugs, a home blood test
collection kit, an oral diagnostic test, an HIV antigen test, an HIV-1
antigen test for blood supply, and an HIV viral load test are among the
most recent in a long line of products FDA has approved to prevent,
diagnose and treat infection with HIV, the virus that causes AIDS.


HIV Tests 

The 1992 National Health Interview Survey by the Centers for Disease
Control and Prevention found that only 20 percent of people at increased
risk for HIV infection--such as intravenous drug users, male
homosexuals, and prostitutes--agreed to be tested for HIV. More than
twice that many people in the same risk group said they might use a home
testing and counseling service if one were available. At the time,
however, testing could only be done by a professional.

The situation changed when, on May 14, 1996, FDA approved Confide, the
first HIV test system with a home-use blood collection kit. A second
test kit was approved last July. It is hoped that home testing will make
diagnosis easier and more accessible, especially in populations among
whom the recent rise in cases of HIV is greatest, such as women, African
Americans, and Hispanics. The tests are highly reliable and are designed
to protect the user's anonymity.

FDA's approval on June 3, 1996, of Orasure Western blot, a laboratory
test that does not require a blood sample, is also expected to increase
participation in testing for HIV. Instead of pricking a finger--a
procedure shunned by many individuals--Orasure uses a treated cotton pad
to collect a tissue sample from between the gum and cheek.

The sample is tested for antibodies to HIV by a procedure that has been
shown to be highly accurate. An earlier version of Orasure used a less
reliable method to screen for HIV antibodies, and people who tested
positive had to undergo a standard blood test to confirm the presence of
the virus.

In March 1996, FDA approved the Coulter HIV-1 p24 Antigen Assay, the
first blood test to detect antigens rather than antibodies. In screening
routinely carried out since the mid-1980s, technicians check donated
blood for HIV-1 antibodies by using enzyme-linked immunosorbent assay
(ELISA) test kits. Since a small number of ELISA test results are
nonspecific or falsely positive, the standard procedure uses a second,
more specific test--the Western blot test--to validate the positive
results from ELISA testing.

The Coulter test, which is used in addition to ELISA, screens blood for
antigens--proteins found on the surface of the virus--that are
detectable about one week earlier than HIV antibodies. The new test
reduces the so-called "window" period, typically up to three months
long, during which standard blood tests show no HIV antibodies, even
though the donor may be infected.

The Amplicor HIV-1 Monitor Test, another new blood test approved last
year, enables physicians to predict the risk of HIV disease progression
by precisely measuring virus levels in blood. The test, which amplifies
copies of genetic material from the virus by using polymerase chain
reaction technology, is based on clinical studies showing that higher
virus levels can be correlated with increased risk that the disease will
progress to AIDS, and AIDS-related infection or death.

Condoms 

Other than abstinence, latex-rubber condoms are the best protection
against sexual transmission of HIV. Latex condoms should always be used
for oral, anal and vaginal sex in any relationship that isn't mutually
monogamous, and if there is any other chance that either partner may be
infected. Condom manufacturers in the United States electronically test
all condoms for holes and weak spots. In addition, FDA requires
manufacturers to use a water test to examine samples from each batch of
condoms for leakage. If the test detects a defect rate of more than 4
per 1,000, the entire lot is discarded.

The agency also encourages manufacturers to test samples of their
products for breakage by using an air burst test in accordance with
specifications of the International Standards Organization.

Under an FDA proposal, the labeling on latex condoms should state that
"this product contains natural rubber latex." FDA has also requested
manufacturers to state on the label that "[if] used properly, latex
condoms will help reduce the risk of transmission of HIV infection
(AIDS) and many other sexually-transmitted diseases."

Consumers should make sure the condom package is undamaged, and check
each condom for damage as it is unrolled to be used. The condom should
not be used if it is gummy or brittle, discolored, or has a hole.
Condoms also should not be used after their expiration date or, if they
don't have an expiration date, more than five years after the date of
manufacture. Only water-based lubricants (for instance, glycerine or K-Y
jelly) should be used with latex condoms, because oil-based lubricants
such as petroleum jelly weaken natural rubber.

For people allergic to latex, FDA has approved several polyurethane
condoms, which have been shown in laboratory tests to be comparable to
latex condoms as a barrier to sperm and HIV virus. Each package of
polyurethane condoms is labeled "For Latex Sensitive Condom Users."
Natural membrane (lambskin) condoms, which are useful in preventing
pregnancy, are not effective protection against HIV or other sexually
transmitted diseases. Although sperm cannot pass through the lambskin
material, small microorganisms, including HIV, can penetrate these
condoms.

One product available for women--the polyurethane Reality Female
Condom--provides limited protection against sexually transmitted
diseases. FDA requires the labeling of Reality to indicate that "highly
effective protection" against STDs is provided if the male partner uses
a latex condom for men. Male and female condoms, however, should not be
used at the same time because they won't stay in place.

Medical and Dental Equipment 

To protect patients and health-care providers against exposure to
potentially contaminated blood and other body liquids, FDA established
quality standards for latex and synthetic rubber gloves used during
surgery and patient examination. U.S. manufacturers of these products
are requested to test samples from each lot to make sure they show no
sign of leakage when filled for two minutes with 1,000 milliliters of
water, and that they meet the standards of the American Society for
Testing and Materials for stress resistance, tensile strength,
materials, and dimensions. FDA also tests samples of domestic and
imported surgical and patient examination gloves, using the same
criteria.

FDA has joined CDC and the American Dental Association in urging
dentists to autoclave--sterilize by steam under pressure--dental hand
pieces and accessories between patients to remove possible contaminants.
In addition, FDA requires that all such equipment must be designed to
withstand autoclaving, and the labeling must include instructions for
the sterilization process.

While most dentists are believed to comply with the recommendations for
autoclaving, it's a good idea to ask what preventive measures the
dentist follows before making an appointment.

Blood Transfusion 

Each year, about 3.6 million Americans receive transfusions of blood
products. FDA inspects the more than 3,000 donor centers where blood and
blood components are collected and processed, and continuously updates
requirements and standards designed to prevent disease transmission
through transfusion.

Blood collection centers and manufacturers and distributors of blood
products are responsible for maintaining five layers of overlapping
safeguards.

First, potential donors must answer questions about their health and
risk factors. Those whose blood may pose a health hazard are encouraged
to exclude themselves. A trained and competent health professional then
interviews potential donors about their medical histories.

Donors can be temporarily excluded from donating blood for such reasons
as having a temperature, cold, cough, or sore throat on the day of the
donation. Potential donors are permanently excluded from donating blood
for reasons including evidence of HIV infection, male homosexual
activity since 1977, and a history of intravenous drug abuse or viral
hepatitis.

Second, blood establishments must keep current a list of deferred donors
and check donor names against that list.

Third, after donation, the blood is tested for such blood-borne agents
as HIV, hepatitis and syphilis.

The fourth layer of protection prevents general use of any blood
products that have not been thoroughly tested.

The fifth layer of protection is FDA's requirement that blood
establishments must investigate any breaches of safeguards and correct
deficiencies. An error or accident can result from improper testing,
incorrectly labeled components, improper interpretation of test results,
improper use of equipment or failure to follow the manufacturers'
directions for its use, or accepting units from donors who should have
been deferred.

The system has helped reduce the risk of transfused HIV infection from 1
in 2,500 units of blood in 1985 to 1 in 440,000 to 640,000 units by the
end of 1995. Since then, the Coulter test has shortened the typical
window period when the HIV virus cannot be detected to less than three
months. Health experts expect the use of this test to reduce the risk of
transfused HIV infection even further.


Human Tissue Transplants 

In December 1993, FDA issued an interim requirement that potential
donors of all human tissues for transplantation--including tendons,
bone, skin, and corneas--be tested for HIV-1, HIV-2, and hepatitis B and
C viruses, and screened for symptoms of AIDS, hepatitis, and high-risk
behaviors such as sex between males and intravenous drug abuse. Imported
tissues must be accompanied by records showing that the tissues were
similarly screened and tested. If such records are not available, the
tissues must be shipped under quarantine.

The agency is preparing a final rule and a guideline to ensure
uniformity in tissue testing and screening.


Drugs 

In December 1995, a new class of drugs called protease inhibitors was
added to the earlier approved class of nucleoside analogs, which
included Retrovir (zidovudine, also known as AZT), Videx (didanosine, or
ddI), Hivid (zalcitabine, or ddC), Zerit (stavudine, or d4t), and Epivir
(lamibudine, or 3TC).

The protease inhibitors--Invirase (saquinavir), Norvir (ritonavir), and
Crixivan (indinavir)--inhibit replication of HIV in a similar way as
nucleoside analogs, but are active at different points in the
replication process. Tested alone or in combination with the nucleoside
analogs, the three protease inhibitors markedly reduced the viral load
and increased the number of CD4 cells, which sharply declines in HIV
infection and AIDS.

In June 1996, FDA approved Viramune (nevirapine), the first in a new
class of drugs called non-nucleoside reverse transcriptase inhibitors.
Viramune was approved for use in combination with nucleoside analogs to
treat adults with HIV infection who have experienced clinical and/or
immunological deterioration.

By the end of June, FDA also had approved 22 drugs for HIV- and
AIDS-related conditions. Among them are NebuPent (aerosolized
pentamidine isethionate) to prevent Pneumocystis carinii pneumonia, the
most common life-threatening infection of people with AIDS, and
Roferon-A (interferon alfa-2a) and Intron-A (interferon alfa-2b) for
Kaposi's sarcoma, an aggressive cancer that affects primarily male
homosexuals with AIDS.


Nutrition 

Some patients with HIV have wasting syndrome, with symptoms that include
major weight loss, chronic diarrhea or weakness, and constant or
intermittent fever for at least 30 days. The syndrome is classified as
an AIDS-defining illness. All people with HIV should carefully follow
food safety practices, because their weakened immunity leaves them
particularly vulnerable to food-borne illness. Diarrhea caused by such
illness can lead to or worsen wasting syndrome.

To prevent food-borne illnesses, people with HIV should avoid
nonpasteurized dairy products, wash hands and utensils with soap and hot
water when preparing meals, and cook food thoroughly to kill harmful
bacteria. Raw eggs and raw seafood such as oysters, clams, sushi, and
sashimi should not be eaten. Additional information about food safety
and HIV can be obtained from FDA.

Loss of appetite (anorexia) can be treated with two FDA-approved
prescription medicines for HIV and AIDS patients. Marinol (dronabinol),
a synthetic extract of marijuana, is indicated for anorexia associated
with weight loss. Megace (megestrol acetate) can be used for anorexia,
cachexia (emaciation), or any unexplained significant weight loss.

Unapproved Therapies 

Recognizing the special needs of people with HIV infection and AIDS, FDA
uses its discretion to allow them to import for their personal use
unapproved but promising drugs for HIV and HIV-related life-threatening
diseases. At the same time, the agency vigorously campaigns against AIDS
health scams that have bilked their victims of as much as $ 10 billion a
year.

As a result of FDA investigations, federal and state authorities have
taken legal actions against individuals involved in hundreds of
fraudulent cures for AIDS such as "energized" water, "ozone therapy,"
and hydrogen peroxide "treatment."

Because most of the scams are local enterprises, FDA initiated in 1989
an AIDS Health Fraud Task Force Network to monitor and counter the
promotion of suspected fraudulent AIDS products. The task forces, so far
established in 10 states, have built broadly based coalitions of
federal, state and local authorities with the medical community and AIDS
activists. They cooperate in explaining to individuals and organizations
how to identify fraudulent health products and distribute general
information about HIV infection.


Mike Kubic is a member of FDA's public affairs staff. 

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


For More Information

To learn more about food safety and HIV, write to FDA (HFE-88), 5600
Fishers Lane Rockville, MD 20857, and ask for the brochure "Eating
Defensively--Food Safety Advice for Persons with AIDS." Be sure to
include the publication number: (FDA) 92-2232. More information about
AIDS and HIV is also available from FDA's Office of AIDS and Special
Health Issues on the World Wide Web.

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


Second Skins

by Carolyn J. Strange

Last spring, a 68-year-old Northern California man suffered deep,
third-degree burns when he dropped a cigarette and his pants leg caught
fire. Unfortunately, such injuries are all too common. What's unusual is
that this man became the first patient treated outside clinical trials
with a new artificial skin that the Food and Drug Administration had
just approved for marketing the month before.

A serious burn is one of the most horrendous traumas the body can
suffer. Every year, about 51,000 Americans are hospitalized for burn
treatment, according to the American Burn Association, and 5,500 die.
The good news is that the incidence and severity of burn injuries have
declined significantly over the past 20 years. And patient survival
keeps improving.

"This is a very exciting area," says Charles Durfor, Ph.D., in FDA's
division of general and restorative devices. "Thirty to forty years ago,
many burn patients didn't live. Advances in treatment have created a
whole new patient population that not only lives, but has an improving
quality of life."

The first great strides were in getting patients through the initial
shock, and preventing fluid loss. Controlling infection, a serious
threat to burn patients, also improved. Specialized nutritional support
has helped. Another leap occurred when doctors began surgically
removing, or excising, all burned tissue from the wound as soon as
possible. After stabilizing the patient and cleaning out the wound, the
next step is to cover it.

"The sooner you close the wound, the sooner the patient gets better,"
says Robert Klein, M.D., medical director of the regional burn center at
Children's Hospital Medical Center of Akron, Ohio.


"The problem is, we've never had an optimal way to do it," says Jerold
Kaplan, M.D., director of the burn centers at Alta Bates Hospital in
Berkeley, Calif., and at Children's Hospital in nearby Oakland. The need
to cover wounds as quickly as possible while minimizing scarring and
additional trauma has driven development of advanced wound dressings and
skin substitutes. Kaplan treated the 68-year-old California man's wounds
with Integra Artificial Skin Dermal Regeneration Template, from Integra
LifeSciences Corp., Plainsboro, N.J. "Integra is a significant addition
to the armamentarium of the burn surgeon," Kaplan says, and other
surgeons agree.


Skin Deep 

Surgeons also agree that no single product or technique is right for
every burn situation. And so far, there's no true replacement for
healthy, intact skin, which is the body's largest organ, and one of the
most complex. It's the first line of defense against infection and
dehydration, but it's more than just a physical barrier. Skin also helps
control temperature, through adjustments of blood flow and evaporation
of sweat. It's an important sensory organ, too.

Skin thickness varies with age and body location, but averages only 1 to
2 millimeters (0.04 to 0.08 inches) thick. Thick or thin, it has two
layers. The thin outer epidermis is nourished from the thicker, more
sensitive dermis below. The outermost surface is a tough, protective
coating of dead, flat cells resembling paving stones. As these cells
wear away, they're replaced from beneath. The innermost part of the
epidermis consists of rapidly dividing cells, called keratinocytes,
which produce keratin, a tough protein. Epidermis also contains a unique
fatty substance that makes skin waterproof.

The skin's blood vessels, lymph vessels, and nerves are in the dermis.
Hair follicles, sweat glands, and oil glands also reside deep in this
layer, which is mainly connective tissue. A network of collagen, the
most common protein in the body, gives flexibility and structural
support to the skin. Fibroblasts are the dominant cell type. Dermis
plays a role in preventing wound contraction and scarring.

Treatment of burns depends on how deep and extensive they are, and the
overall health of the patient. First-degree burns (such as sunburns)
affect only the epidermis; they may peel but generally heal quickly.
Second-degree burns damage the skin more deeply, causing blisters but
sparing some of the dermal layer. Unless they're extensive, these burns
usually heal without serious scarring. Third-degree burns destroy the
full skin thickness, sometimes exposing muscle or bone, and require
specialized treatment and skin grafts to obtain complete wound healing
and reduce scarring. Left alone, the body tries to close wounds quickly
by contraction, which results in serious scarring that is not only
disfiguring, but can also be disabling.

Currently, the best wound covering most often is the patient's own skin.
Healthy skin from another body site can be transplanted, which is called
an autograft (autos means self). Sometimes little slits are cut so the
resulting meshed graft can be stretched to cover more area. A
split-thickness graft takes only the upper skin layer, and the donor
site usually heals within several days. The thinner the graft, the
faster the donor site heals. Surgeons may even take additional thin
grafts from healed sites. Full-thickness grafts usually give a
better-looking final result, but sometimes they don't adhere and
survive. Donor sites are limited and autografting isn't always possible.

"People with great big burns don't have enough of their own skin, so you
have to have some other way of covering them," says David M. Heimbach,
M.D., director of the University of Washington Burn Center at
Harborview, Seattle. Some patients can't withstand the additional trauma
of a donor site wound. Older patients heal slowly and have thinner skin
to begin with. And grafting creates another scar.

Doctors often use temporary coverings while patients get stronger, or
while donor sites heal for additional harvesting. Two traditional
possibilities are an allograft (allos means other) of human skin,
usually cadaver skin, or a xenograft (xenos means stranger, in this case
from another species) of pig skin. Cadaver skin is preferable, but as
with other donated organs, sometimes it's in short supply and
transmission of infectious agents is a concern. Human skin is regulated
under FDA's Human Tissue Program, which requires donor screening for HIV
(the AIDS virus) and hepatitis. In any case, the immune system rejects
allo- and xenografts in a matter of days or weeks, and they must be
removed and replaced. To avoid such problems, researchers and
manufacturers are developing better wound dressings.


Advanced Dressings 

DA recognizes two broad categories of wound dressings--interactive and
noninteractive. A variety of noninteractive dressings are available for
covering first- and second-degree burns and other wounds. An interactive
dressing is intended to actively promote wound healing by interacting
directly with body tissues. Manufacturers must submit safety and
effectiveness data to FDA in a premarket approval application. FDA has
approved two interactive wound dressings for use on third-degree burns:
Integra Artificial Skin and Original BioBrane (Blue Label), marketed by
Dow B. Hickam, Inc., New York.

BioBrane is a knitted nylon fabric bonded to an ultra-thin silicone
rubber membrane coated with a protein (gelatin) derived from pig tissue.
Clotting factors in the wound interact with the gelatin in the dressing,
causing it to adhere to the wound within a day or so. The dressing
remains in place until autografting becomes possible.

Integra is a two-layer membrane--a dermal layer that's a porous lattice
of cross-linked collagen fibers, and a synthetic epidermal layer. The
dermal layer acts as a biodegradable template that helps organize dermal
tissue regeneration. Fibroblasts and other cells migrate into the
lattice from surrounding healthy tissue, as do blood and lymph vessels.
The fibroblasts degrade the temporary scaffold and recreate their own
collagen matrix.

"The dermal part of the product is a permanent cover which the body
converts into something which looks more like dermis than it looks like
scar tissue," Heimbach says.

The outer synthetic layer provides the barrier functions of epidermis
for two to three weeks; then the surgeon replaces it with a very thin
autograft. "The ability to have the donor site be very thin and heal in
just a few days is the big benefit," says Kaplan. "You're actually
adding a procedure, but the end result is positive."

"It's a neat concept and it appears to work," says Heimbach, who has
used Integra on more than 100 patients during clinical trials. He says
the final results look much better than the alternative, meshed
autografts. "We're excited about the new composite skin substitutes," he
says.

Cultured Skin 

Doctors prefer a thin graft to a thick one, but eliminating the donor
site wound and scar altogether would be even better. That's done by
growing the patient's skin in the lab, under special tissue culture
conditions. Lab-grown skin products also have other potential uses for
wounds other than burns, and for laboratory testing. (See accompanying
articles.) From a postage stamp-sized piece of skin, technicians can
grow enough skin in about three weeks to nearly cover the body. Some
medical centers are equipped for this sort of cell culture, and Genzyme
Tissue Repair, Cambridge, Mass., does it as a commercial service.
Cultured skin has been available for treating burns for about a decade,
and in certain circumstances it can work well.

"The problem here is you're putting on epidermis and not dermis," Kaplan
says.

"Without both parts, you don't really have skin," Heimbach says. "You're
grafting on scar tissue and that's not a satisfactory skin covering."

Less than 10 cells thick, it's also tricky to handle. "It's like
gossamer," Kaplan says. And something has to cover the wound in the
meantime. That's where Kaplan and others see a potentially useful
combination. The patient's epidermis could be cultured during the two to
three weeks while Integra's dermal layer becomes a suitable bed for
grafting. "They're complementary," says Kaplan.

"You'd have the best of both worlds. You don't have any donor sites, and
you have a good, durable, cosmetically acceptable cover," says Heimbach.

"Another approach we're actively working on is the one-step procedure,"
says Frederick Cahn, Ph.D., senior vice president, technology, Integra
LifeSciences. The patient's own epidermal cells are isolated, as they
would be for culturing, then seeded onto the dermal layer of Integra
before it is applied to the wound. Both skin layers regenerate in place
simultaneously, and only one surgical procedure is required. This
procedure has worked well in animals, but hasn't been tried in humans
yet.

Although physicians welcome new ways to help their patients, they're
leery of "scar in a jar" products that might solve some problems while
creating others. Last year, FDA held hearings on using the patient's own
cells for structural repair in therapy, and heard a strong call for
measures of efficacy. Based on the testimony presented, FDA has decided
to regulate such therapy and is developing guidance documents to assist
manufacturers in completing the premarket review process.

"FDA recognizes that the area of tissue substitutes is a rapidly
evolving area--and that medical and biochemical practice are also
growing rapidly--and it's working aggressively to make sure it doesn't
stifle development while continuing to ensure patient safety," says
FDA's Durfor.

Investigators have developed other variations on cultured skin in the
hope of providing off-the-shelf, living, temporary or permanent
dressings. Clinical trials are under way testing them on burns and other
wounds. For example, Advanced Tissue Sciences, La Jolla, Calif.,
developed its Dermagraft-TC skin replacement to be used as an
alternative to cadaver skin for burns.

Treatment for burns keeps improving, but burn surgeons still have
another important concern. "I think 95 percent of the burns we see are
completely preventable," says Heimbach. He credits smoke detectors for a
huge drop in the number of burns and deaths from house fires, but he
hasn't seen much change in the number of accidents caused by
carelessness or ignorance.

"The answer to the burn problem is prevention. Once it happens, it's too
late," Klein says. "Be careful so you never need us."

Carolyn J. Strange is a science and medical writer living in Northern
California. 

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


Hope for Wounds That Won't Go Away

It may be hard for a healthy person to imagine having a wound that just
won't heal, but that problem plagues millions of Americans. Nonhealing
wounds not only take an emotional toll, but also leave patients, their
families, and society with a serious economic burden, ranging into
billions of dollars.

The incidence of chronic wounds is far greater than burns and is
expected to continue to increase as the population ages. Some of the
treatment concerns are similar because the barrier function of skin is
lost, putting the patient at risk for infection, and chronic wounds can
be life threatening.

There are three general types of chronic wounds: pressure ulcers
(bedsores or decubitus ulcers), venous ulcers, and diabetic ulcers. They
have different causes, but the result is the same--localized tissue
death. The factors that cause an ulcer to develop in the first place
also interfere with healing. The cost per healed ulcer--when they heal
at all--can climb into the tens of thousands of dollars, and as many as
half recur within a year. Roughly three-quarters of a million American
diabetics suffer with foot ulcers, which are responsible for more than
50,000 amputations a year.


Recent research efforts in pursuit of various growth factors to promote
wound healing have been disappointing. Figuring out which growth factors
to put in a wound--and when and at what dose--is a daunting, perhaps
impossible, task. Some investigators have turned to cultured skin,
arguing that applying cultured skin to wounds makes more sense than
using growth factors because living cells already know how to produce
growth factors at the right time and in the right amount.

Organogenesis Inc., of Canton, Mass., has developed Apligraf (formerly
Graftskin), a two-layer living skin substitute derived from infant
foreskins. The upper layer contains keratinocytes, the dominant cell
type in the epidermis. The lower layer contains collagen and
fibroblasts, the main constituents of dermis. Other cell types that
trigger immunological response are absent, and, as a result, this
engineered tissue is not rejected. Human trials of Apligraf for treating
burns, diabetic ulcers, and for use in other skin surgeries are under
way.

Cultured skin offers new hope for chronic wounds, but, as with burns,
prevention is the best bet.

--C.J.S. 


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


Skin Under Glass

In addition to its potential as an advanced wound dressing, cultured
skin may also prove useful in laboratory testing. Many cosmetic,
household product, pharmaceutical, and petrochemical companies are
experimenting with cultured skin in the hope that in vitro (in glass,
meaning in lab vessels) assays can replace or reduce animal testing for
evaluating raw materials and final product formulations. FDA has long
supported development of such methods, but the state of the science
hasn't progressed yet to where it can fully replace animal testing,
according to FDA's John Bailey, who heads the Office of Cosmetics and
Colors in the agency's Center for Food Safety and Applied Nutrition.

Scientists can use isolated skin tissue to test skin penetration,
irritation, toxicity, and other effects of various substances. Although
cadaver skin works for some purposes, its uses are limited because the
cells are dead. Cultured skin contains live, metabolizing cells that can
better mimic how skin responds to various stimuli.

One example is the EpiDerm System, a model of human epidermis marketed
by MatTek Corp., Ashland, Mass. Human-derived epidermal cells are grown
under culture conditions that encourage formation of the characteristic
cell subtypes and layers of epidermis. Another example is Skin2 ,
developed by Advanced Tissue Sciences, Inc., La Jolla, Calif. Some
versions of Skin2 contain dermis as well as epidermis. These products
are intended to be used for testing, not as dressings.

Lab-grown skin is used in two general ways. As a membrane to measure
skin absorption, it doesn't work very well because it's much more
permeable than skin, according to Robert L. Bronaugh, Ph.D., chief of
the skin absorption and metabolism section in FDA's Office of Cosmetics
and Colors. "A lot more work needs to be done before it can be used to
simulate accurately the barrier properties of human skin," he says.

However, as an alternate test to measure irritation, cultured skin looks
encouraging, according to Bronaugh. The U.S. Department of
Transportation has approved the use of a Skin2 in vitro test kit as an
alternative to animal testing of potentially corrosive materials.
Although FDA wouldn't accept final safety data acquired from these in
vitro assays, companies can use cultured skin in early screenings, and
that saves animals, as well as money.


--C.J.S. 


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


Overcoming Infertility

by Tamar Nordenberg

Myth or fact: If a couple is having trouble conceiving a child, the man
should try wearing loose underwear? That's a fact, according to a study
on "Tight-fitting Underwear and Sperm Quality" published June 29, 1996,
in the scientific journal The Lancet. Tight-fitting underwear--as well
as hot tubs and saunas--is not recommended for men trying to father a
child because it may raise testes temperature to a point where it
interferes with sperm production.

But couples having difficulty getting pregnant can tell you the solution
is almost never as simple as wearing boxers instead of briefs. Lisa (who
asked that her last name not be used) tried for more than two years to
get pregnant without success. "Everyone gave me advice," she says. "My
mother said I should just go to church and pray more. My friends said,
'Try to relax and not think about it' or 'You're just overstressed. You
work too much.'"

Actually, psychological stress is more likely a result of infertility
than the cause, according to Resolve, a nonprofit consumer organization
specializing in infertility.

"Fertility problems are a huge psychological stressor, a huge
relationship stressor," says Lisa Rarick, M.D., director of the Food and
Drug Administration's division of reproductive and urologic drug
products.

So, while going on a relaxing vacation may temporarily relieve the
stress that comes with fertility problems, a solution may require
treatment by a health-care professional. Treatment with drugs such as
Clomid or Serophene (both clomiphene citrate) or Pergonal, Humegon or
Metrodin (all menotropins) are used in some cases to correct a woman's
hormone imbalance. Surgery is sometimes used to repair damaged
reproductive organs. And in about 10 percent of cases, less
conventional, high-tech options like in vitro fertilization are used.

Will the therapies work? "Talking about the success rate for fertility
treatments is like saying, 'What's the chance of curing a headache?'"
according to Benjamin Younger, M.D., executive director of the American
Society for Reproductive Medicine. "It depends on many things, including
the cause of the problem and the severity." Overall, Younger says, about
half of couples that seek fertility treatment will be able to have
babies.

A Year Without Pregnancy 

[diagram illustrating the process of fertilization omitted]

Infertility is defined as the inability to conceive a child despite
trying for one year. The condition affects about 5.3 million Americans,
or 9 percent of the reproductive age population, according to the
American Society for Reproductive Medicine.

Ironically, the best protection against infertility is to use a condom
while you are not trying to get pregnant. Condoms prevent sexually
transmitted diseases, a primary cause of infertility.

Even a completely healthy couple can't expect to get pregnant at the
drop of a hat. Only 20 percent of women who want to conceive become
pregnant in the first ovulation cycle they try, according to Younger.

To become pregnant, a couple must have intercourse during the woman's
fertile time of the month, which is right before and during ovulation.
Because it's tough to pinpoint the exact day of ovulation, having
intercourse often during the approximate time maximizes the chances of
conception.

After a year of frequent intercourse without contraception that doesn't
result in pregnancy, a couple should go to a health-care professional
for an evaluation. In some cases, it makes sense to seek help for
fertility problems even before a year is up.

A woman over 30 may wish to get an earlier evaluation. "At age 30, a
woman begins a slow decline in her ability to get pregnant," says
Younger. "The older she gets, the greater her chance of miscarriage,
too." But a woman's fertility doesn't take a big drop until around age
40.

"A man's age affects fertility to a much smaller degree and 20 or 30
years later than in a woman," Younger says. Despite a decrease in sperm
production that begins after age 25, some men remain fertile into their
60s and 70s.

A couple may also seek earlier evaluation if:

 * The woman isn't menstruating regularly, which may indicate an absence
   of ovulation that would make it impossible for her to conceive
   without medical help.

 * The woman has had three or more miscarriages (or the man had a
   previous partner who had had three or more miscarriages).

 * The woman or man has had certain infections that sometimes affect
   fertility (for example, pelvic infection in a woman, or mumps or
   prostate infection in a man).

 * The woman or man suspects there may be a fertility problem (if, for
   example, attempts at pregnancy failed in a previous relationship).


The Man or the Woman? 

Impairment in any step of the intricate process of conception can cause
infertility. For a woman to become pregnant, her partner's sperm must be
healthy so that at least one can swim into her fallopian tubes. An egg,
released by the woman's ovaries, must be in the fallopian tube ready to
be fertilized. Next, the fertilized egg, called an embryo, must make its
way through an open-ended fallopian tube into the uterus, implant in the
uterine lining, and be sustained there while it grows. (See diagram.)

It is a myth that infertility is always a "woman's problem." Of the 80
percent of cases with a diagnosed cause, about half are based at least
partially on male problems (referred to as male factors)--usually that
the man produces no sperm, a condition called azoospermia, or that he
produces too few sperm, called oligospermia.

Lifestyle can influence the number and quality of a man's sperm. Alcohol
and drugs--including marijuana, nicotine, and certain medications--can
temporarily reduce sperm quality. Also, environmental toxins, including
pesticides and lead, may be to blame for some cases of infertility.

The causes of sperm production problems can exist from birth or develop
later as a result of severe medical illnesses, including mumps and some
sexually transmitted diseases, or from a severe testicle injury, tumor,
or other problem. Inability to ejaculate normally can prevent
conception, too, and can be caused by many factors, including diabetes,
surgery of the prostate gland or urethra, blood pressure medication, or
impotence.

The other half of explained infertility cases are linked to female
problems (called female factors), most commonly ovulation disorders.
Without ovulation, eggs are not available for fertilization. Problems
with ovulation are signaled by irregular menstrual periods or a lack of
periods altogether (called amenorrhea). Simple lifestyle
factors--including stress, diet, or athletic training--can affect a
woman's hormonal balance. Much less often, a hormonal imbalance can
result from a serious medical problem such as a pituitary gland tumor.

Other problems can also lead to female infertility. If the fallopian
tubes are blocked at one or both ends, the egg can't travel through the
tubes into the uterus. Such blockage may result from pelvic inflammatory
disease, surgery for an ectopic pregnancy (when the embryo implants in
the fallopian tube rather than in the uterus), or other problems,
including endometriosis (the abnormal presence of uterine lining cells
in other pelvic organs).

A medical evaluation may determine whether a couple's infertility is due
to these or other causes. If a medical and sexual history doesn't reveal
an obvious problem, like improperly timed intercourse or absence of
ovulation, specific tests may be needed.

Tests for Both 

The man's evaluation focuses on the number and health of his sperm. The
laboratory first examines a sperm sample under a microscope to check
sperm number, shape and movement. Further tests may be needed to look
for infection, hormonal imbalance, or other problems.

Male tests include:

 * X-ray: If damage to one or both of the vas deferens (the ducts in the
   male that transport the sperm to the penis) is known or suspected, an
   x-ray is taken to examine the organs.

 * Mucus penetrance test: Test of whether the man's sperm are able to
   swim through a drop of the woman's fertile vaginal mucus on a slide
   (also used to test the quality of the woman's mucus).

 * Hamster-egg penetrance assay: Test of whether the man's sperm will
   penetrate hamster egg cells with their outer cells removed,
   indicating somewhat their ability to fertilize human eggs.

For the woman, the first step in testing is to determine if she is
ovulating each month. This can be done by charting changes in morning
body temperature, by using an FDA-approved home ovulation test kit
(which is available over the counter), or by examining cervical mucus,
which undergoes a series of hormone-induced changes throughout the
menstrual cycle.

Checks of ovulation can also be done in the physician's office with
simple blood tests for hormone levels or ultrasound tests of the
ovaries. If the woman is ovulating, further testing will need to be
done.

Common female tests include:

 * Hysterosalpingogram: An x-ray of the fallopian tubes and uterus after
   they are injected with dye, to show if the tubes are open and to show
   the shape of the uterus.

 * Laparoscopy: An examination of the tubes and other female organs for
   disease, using a miniature light-transmitting tube called a
   laparoscope. The tube is inserted into the abdomen through a one-inch
   incision below the navel, usually while the woman is under general
   anesthesia.

 * Endometrial biopsy: An examination of a small shred of uterine lining to
   see if the monthly changes in the lining are normal.

Some tests require participation of both partners. Samples of cervical
mucus taken after intercourse can show whether sperm and mucus have
properly interacted. Also, a variety of tests can show if the man or
woman is forming antibodies that are attacking the sperm.

Drugs and Surgery

Depending on what the tests turn up, different treatments are
recommended. Eighty to 90 percent of infertility cases are treated with
drugs or surgery.

Therapy with the fertility drug Clomid or with a more potent hormone
stimulator--Pergonal, Metrodin or Humegon--is often recommended for
women with ovulation problems. The benefits of each drug and the side
effects, which can be minor or serious but rare, should be discussed
with the doctor. Multiple births occur in 10 to 20 percent of births
resulting from fertility drug use.

Other drugs, used under very limited circumstances, include Parlodel
(bromocriptine mesylate), for women with elevated levels of a hormone
called prolactin, and a hormone pump that releases gonadotropins
necessary for ovulation.

If drugs aren't the answer, surgery may be. Because major surgery is
involved, operations to repair damage to the woman's ovaries, fallopian
tubes, or uterus are recommended only if there is a good chance of
restoring fertility.

In the man, one infertility problem often treated surgically is damage
to the vas deferens, commonly caused by a sexually transmitted disease,
other infection, or vasectomy (male sterilization).

Other important tools in the battle against infertility include
artificial insemination and the so-called assisted reproductive
technologies. (See accompanying article.)

Fulfillment Regardless

Lisa became pregnant without assisted reproductive technologies, after
taking ovulation-promoting medication and undergoing surgery to repair
her damaged fallopian tubes. Her daughter is now 4 years old.

"It was definitely worth it. I really appreciate having my daughter
because of what I went through," she says. But Lisa and her husband
won't try to have a second child just yet. "At some point you have to
stop trying to have a baby, stop obsessing over what might be an
unreachable goal," she says.

When having a genetically related baby seems unachievable, a couple may
decide to stop treatment and proceed with the rest of their lives. Some
may choose to lead an enriched life without children. Others may choose
to adopt.

And no, according to Resolve, you're not more likely to get pregnant if
you adopt a baby.

To get more information about infertility, send a self-addressed stamped
envelope to: Resolve, 1310 Broadway, Somerville MA 02144-1731, or call
their National Helpline at (617) 623-0744.

Tamar Nordenberg is a staff writer for FDA Consumer.
------------------------------------------------------------------------


Science and ART

Sometimes it may be necessary or preferable to get pregnant without
intercourse. A woman may choose to get pregnant with the sperm of
someone who is not her partner.

In some cases, a woman may not be able to become pregnant with her
partner because his sexual problems make it impossible for him to
ejaculate normally during sex, or because the sperm have to bypass the
vagina if the vaginal mucus cannot support them, or for other reasons.
In these cases, through artificial insemination, the semen is placed
into the woman's uterus or vaginal canal using a hollow, flexible tube
called a catheter.

[diagram illustrating the process of in vitro fertilization omitted]

New, more complex assisted reproductive technologies, or ART,
procedures, including in vitro fertilization (IVF), have been available
since the birth 18 years ago of Louise Brown, the world's first "test
tube baby." IVF makes it possible to combine sperm and eggs in a
laboratory for a baby that is genetically related to one or both
partners.

IVF is often used when a woman's fallopian tubes are blocked. First,
medication is given to stimulate the ovaries to produce multiple eggs.
Once mature, the eggs are suctioned from the ovaries (1) and placed in a
laboratory culture dish with the man's sperm for fertilization (2). The
dish is then placed in an incubator (3). About two days later, three to
five embryos are transferred to the woman's uterus (4). If the woman
does not become pregnant, she may try again in t he next cycle.

Other ART procedures, based on many of the same principles, include:

 * Gamete intrafallopian transfer, or GIFT: Similar to IVF, but used
 when the woman has at least one normal fallopian tube. Three to five
 eggs are placed in the fallopian tube, along with the man's sperm, for
 fertilization inside the woman's body.

 * Zygote intrafallopian transfer, or ZIFT (also called tubal embryo
 transfer): A hybrid of IVF and GIFT. The eggs retrieved from the
 woman's ovaries are fertilized in the lab and replaced in the fallopian
 tubes rather than the uterus.

 * Donor egg IVF: For women who or example, have impaired ovaries or
 carry a genetic disease that can be transferred to the offspring. Eggs
 are donated by another healthy woman and fertilized in the lab with the
 male partner's sperm before being transferred to the female partner's
 uterus.

 * Frozen embryos: Excess embryos are frozen, to be thawed in the future
 if the woman doesn't get pregnant on the first cycle or wants another
 baby in the future.

New treatments for male factors are fast-evolving. Intracytoplasmic
sperm injection is one of the most exciting new procedures, according to
Benjamin Younger, M.D., executive director of the American Society for
Reproductive Medicine. A single egg is injected with a single sperm to
produce an embryo that can implant and grow in the uterus.

About two-thirds of births from ART procedures are single births. Of the
rest, almost all are twins, with about 6 percent resulting in the birth
of triplets or more.

--T.N. 

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

Breast Reduction Often Good Medicine

by Marilynn Larkin 

Breast size usually isn't considered an appropriate topic for social
conversation. But for a woman suffering the medical and social
consequences of having large, pendulous breasts, talking with someone
who has undergone breast reduction can be a "life-changing experience,"
says Mary-Margaret Richardson, a public affairs specialist with the Food
and Drug Administration in St. Louis, Mo.

Before surgery, Richardson, 53, had adapted to a "lifetime of
discomfort--bras that never fit and caused deep grooves in my shoulders,
plus neck and back pain, heat rashes under my breasts in the summer, and
ever-increasing stooping under the weight of them."

After talking with Kellie Feldman, a neighbor who had undergone breast
reduction, Richardson decided to have the procedure done herself. "I had
gone for a cancer screening several months earlier, and the doctor who
did the examination looked at my rutted shoulders and asked whether I
had ever thought of having reduction. The seed was planted then,"
Richardson said. "Then I talked with Kellie, and she was so positive
about it."

Feldman, 27, is a special education teacher in St. Louis. "Actually, my
father had been encouraging me to have the surgery," she says. "I was a
bit put off, wondering why he was looking at my breasts. But he said
that when I got older, they would look terrible. And I knew I already
had deep shoulder indentations from my bra. In addition, the male
students in school were always looking and commenting, which made me
feel uncomfortable."

Margie, 40, an advertising executive in New York City who asked that her
last name not be used, had a very different reason for undergoing breast
reduction. "I have breast cancer and had a mastectomy on my right breast
and then an implant," she says. "My surgeon recommended reduction for
the left breast so that it would look more like the right."

Medical Concerns 

Although very different from one another, these women share a mix of
medical problems and cosmetic concerns that led them--and thousands of
other women across the country--to undergo breast reduction surgery. "I
can move my head and neck without pain, my shoulders have healed, and I
just feel so much better," says Richardson. "I think about my
grandmother, who had this problem all her life and was always stooped in
pain. I wish she could have had something like this done then."

"Among my patients, I find there are certain age clusters with similar
concerns," says George Beraka, M.D., a board-certified plastic and
reconstructive surgeon who is assistant professor of surgery at Cornell
Medical Center in New York City.

"Those in their late teens realize they don't want to live with such
large breasts. Women who have finished childbearing and breast-feeding
say to themselves, 'Now I'd like to look and feel better.' And older
women often are referred by their internists because of neck and back
pain."

In some women, breast examination and mammography may be easier to
perform after reduction. "From the standpoint of the physical exam, it
may be more difficult to pick up a very small lesion [lump] in a woman
with very large breasts," says Charles Finder, M.D., a radiologist in
FDA's Mammography Quality and Radiation Program. "Imaging large breasts
for mammography may be a bit more technically demanding, since the
technician may have to get each view done twice, or do two images per
view."

Richardson notes that she "kept getting abnormal mammograms with 'dense
tissue' reports that made me think I had breast cancer." She is "looking
forward to a normal result this time."

But Finder cautions that this may not be the case. "If the breasts are
reduced uniformly, then the tissue may still be dense, and she could
still have problems with mammography," he says.

Contraindications to the procedure "would apply to any major elective
surgery," says Beraka. "The woman should not have any significant
illness, either physical or mental."

Patricia McGuire, M.D., a board-certified plastic and reconstructive
surgeon on staff at Parkcrest Surgical in St. Louis, says she prefers
not to perform breast reduction on women who are heavy smokers because
of a loss of blood supply, or on those with diabetes, since they may not
heal well. Also, "if a woman is really overweight, I encourage her to
get her weight down first. This is particularly a problem with teens
with large breasts, since they may try to gain weight so that their
bodies look more balanced," says McGuire, who performed the reductions
for Richardson and Feldman.

Both physicians believe it is best to wait until a young woman's breasts
are fully grown, usually by age 18, before doing a reduction. The
procedure is not recommended for women who intend to breast-feed,
according to the American Society of Plastic and Reconstructive
Surgeons. 

Breast Cancer

Concerns that breast reduction might increase the risk of breast cancer
are unfounded, according to Beraka. "There are no data to suggest that
women who undergo breast reduction are at greater risk for breast
cancer, or that those with a family history of breast cancer should not
have the procedure," says Beraka. "In fact, reduction is like a giant
biopsy of the breast, because all tissue that is removed during surgery
is examined by a pathologist."

During 20 years of performing the procedure, Beraka says, malignant
tissue was found among his patients "maybe half a dozen times." McGuire,
who has been performing reductions for five years, had one patient in
whom cancerous tissue was discovered.

Preparing for Surgery 

During the initial consultation, the surgeon explains the surgery in
detail, including risks, limitations and scarring, which is an
inevitable consequence of the procedure. The surgeon also discusses
where the surgery will take place, how long the woman will remain in the
facility, any steps that need to be taken preoperatively, and what to
expect postoperatively. Any questions a woman has are answered at this
time.

In preparation for surgery, the woman has a complete physical
examination. The surgeon measures the woman's breasts and usually
photographs them for reference during surgery and afterwards. These
photographs can also serve as documentation for insurance purposes.

Unlike a rhinoplasty (nose reduction), in which computer imaging may be
used to show a prospective patient what her nose is likely to look like
after surgery, the new breast size and shape, as well as positioning of
the nipple and areola (the darker skin around the nipple), are usually
determined during a discussion between the physician and patient.

"Preoperative imaging of any sort is of limited value for this
procedure. It's a marketing tool more than anything else," says Beraka.
"After assessing the size of the breasts, I ask the patient how much
smaller she would like them, taking into consideration what makes sense
in terms of the rest of her body. I then estimate how much tissue will
need to be removed."

Most surgeons provide guidelines for eating, drinking, smoking, taking
medication, and other activities before surgery. Generally, the patient
should not take aspirin or similar medications for a week or two before
surgery, since these medications may lead to increased bleeding. Beraka
suggests women take 1,000 milligrams of vitamin C daily to promote
healing, but avoid vitamin E supplements, which may also lead to
increased bleeding.

If a patient smokes, she may be advised to stop. This is always a good
idea, but it's especially important when general anesthesia is used,
since smoking limits the amount of oxygen the body has available during
surgery and recovery.

Because the size, shape, and amount of tissue in the breast will change
after reduction, most women are advised to have a preoperative mammogram
and a postoperative mammogram six months to a year after surgery for
comparison.

The Surgery 

Breast reduction is generally done on an inpatient basis. The procedure
itself usually takes from two to four hours and requires an overnight
stay in the hospital. In most cases, surgery is performed under general
anesthesia. Generally, breast reduction involves the removal of fat,
glandular tissue, and skin from the breasts; in some cases, the areola
may also be reduced.

Surgical techniques vary, but according to the American Society of
Plastic and Reconstructive Surgeons, "the most common procedure involves
an anchor-shaped incision that circles the areola, extends downward, and
follows the natural curve of the crease beneath the breast." After
removing excess tissue and moving the nipple and areola into their new
positions, the surgeon then "brings the skin from both sides of the
breast down and around the areola, shaping the new contour of the
breast."

[three steps in typical breast reduction surgery, graphic omitted]

The typical procedure is shown at right:

1.The outlined areas show where skin, breast tissue, and fat are
typically removed and how the areola and nipple are repositioned. 2.The
arrows show how skin formerly above the nipple is brought down and
sutured together to reshape the breast. 3.After surgery, scars will
appear around the areola and in the crease under the breast. 

Liposuction (a procedure in which excess fatty tissue is removed from a
specific area of the body by means of a suction device) is sometimes
used to remove excess fat from the armpit area, although some surgeons
also use this procedure to remove excess fatty tissue from the breast.
In some cases, if only fat needs to be removed, liposuction alone may be
used to reduce breast size. The fatty tissue is also reviewed by a
pathologist.


Beraka notes that newer surgical techniques, such as those popularized
by Belgian surgeon Madeleine Lejour, can result in significantly less
scarring around the undersurface of the breast, making the procedure
"less frightening to patients contemplating reduction." However, McGuire
says that while the Lejour technique can be appropriate "for specific
patients," she does not believe it should be used for everyone. "The
scars are shorter, but the surgeon has less control over the shape of
the breast," she says. If the type of incision is important to the
patient, she should discuss it with the surgeon.

Post-Op 

After surgery, "they wrapped me in a bandage to hold everything in
place," Richardson explains. "I was a bit uncomfortable, but I had very
little pain. In fact, I never took anything stronger than extra-strength
acetaminophen during recuperation."

The bandage is removed a couple of days after surgery, after which the
woman wears a surgical bra 24 hours a day for about a month. "I could
shower--I was up and active and doing things," says Richardson.
Nevertheless, she took several weeks off from work to give her body a
chance to recover before resuming a full schedule. Like most women who
undergo reduction, Richardson was advised not to lift or push anything
heavy for three or four weeks.

According to the American Society of Plastic and Reconstructive
Surgeons, the first menstruation following surgery may cause breasts to
swell and hurt, and the woman may also experience shooting pains in her
breasts for several months. Patients may be advised to avoid sex for a
week or so to avoid arousal that can cause the incisions to swell.

"I was relieved that my surgeon has an assistant who answered all my
questions during the recovery period, like 'when will my bruises go
away?' and 'when can I drive again?'" Richardson notes.

Adjusting to Change 

Like most women who undergo reduction, Mary-Margaret Richardson, Kellie
Feldman, and Margie were pleased with the results. "Of all the
procedures I do, this one has the highest patient satisfaction, even
when the results are less than perfect," Beraka says.

"I'm amazed whenever I go shopping. I can buy a dress, not separates
with the top four sizes larger. My posture is so much better, and
there's no rutting in my shoulders. Most of all, the pain in my neck and
back is gone," Richardson says.

"I no longer have rashes under my breasts or shoulder indentations,"
Feldman adds. "Plus, I went on a diet and lost a total of 28 pounds, 7
of which was breast tissue. I feel much healthier."

"People ask, 'why did you wait so long?'" Richardson notes. "I tell them
that when it began to be debilitating, everything sort of came together.
I was scared up until the night before the surgery. But the time was
right. I don't regret one minute of it."

Marilynn Larkin is a medical writer in New York City. 

(The illustration was drawn by Renée Gordon based on information
provided by the American Society of Plastic and Reconstructive
Surgeons.) 

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

Treating Tropical Diseases

by Dixie Farley 

When adventurer Sandra Levy, 61, of Short Hills, N.J., visited Ecuador
and the Galapagos Islands in December 1993, she tried to protect herself
against tropical diseases and the insects that transmit them.

Before leaving home, Levy got vaccinated against yellow fever and took
medicine to ward off malaria.

At the headwaters of the Amazon River, she took precautions. Whether
trekking into the jungle or canoeing across the river to see leaf-eating
ants on the opposite bank, she wore long-sleeved shirts and knee-high
boots and used an insect repellent containing DEET. In her thatch hut at
night, she slept under mosquito netting.

After she returned home, however, Levy noticed a sore the size of a dime
above her left ankle. "It didn't hurt or itch," she says, "but it didn't
go away. I decided to see my dermatologist."

By the end of March, despite antibiotics, her sore had grown to the size
of a silver dollar, so she made another medical appointment. "The doctor
took a biopsy. Knowing I'd been in Ecuador, he had the lab check for
deep fungus and leishmaniasis."

The diagnosis was indeed leishmaniasis, a tropical disease spread by
infected female sandflies. Levy's doctor put her in touch with a
tropical disease specialist for treatment.

As Levy's experience shows, travelers' precautions against tropical
diseases are not foolproof.

"The American public shouldn't be complacent about these diseases," says
Randolph Wykoff, M.D., associate commissioner for operations at the Food
and Drug Administration. "Tropical diseases are absolutely devastating
in other countries, killing hundreds of thousands of people. We are not
immune." While most such infections are acquired during travel, Wykoff
says, some people can also become infected from other travelers who
bring home the disease.

Still, tropical diseases are more prevalent in developing countries,
where conditions all too commonly foster their spread. War refugees
migrating to other areas carry infections with them. Economic and social
crises stress health systems. And unsanitary conditions due to rapid
urbanization and rapid population growth foster an environment in which
insects and other animals can transmit disease-producing organisms.


"King" Malaria 

Sometimes called the King of Diseases, malaria yearly strikes up to 500
million people, 90 percent of them in Africa, with up to 2.7 million
deaths, mostly young children.

Malaria is caused by four species of Plasmodium parasites, transmitted
to humans by infected female Anopheles mosquitoes. Symptoms include a
spiking fever, shaking chills, and flu-like symptoms. Anemia or liver
problems may develop. If treatment is delayed, severe infection may lead
to kidney failure, coma, and death. 

Malaria kills so many African children because they lack immunity, says
tropical disease specialist LTC Alan Magill, M.D., of Walter Reed Army
Institute of Research, Department of Defense. Americans in
Africa--travelers or troops--also are at risk because their immunity to
malaria is like a child's, he says. They have more severe malaria than
Africans who have survived past age 5 and developed immunity. "At our
study site in Kenya," he says, "if you drew blood from 100 seemingly
normal Africans at the local market, you'd find malaria parasites in
most of their bloodstreams. They're infected, and the transmission cycle
goes on, but they don't have obvious ill effects."

The national Centers for Disease Control and Prevention gets about 1,000
reports a year of malaria in the United States. Since 1957, nearly all
these cases were acquired in areas of the world where malaria is known
to occur.

Domestic malaria, in fact, was declared eradicated in this country in
the 1940s. But from 1957 through 1994, CDC got 76 reports of malaria
cases that may have been transmitted locally, including some from
suburban New Jersey in 1991 and New York City in 1993. A 1995 report
from Michigan was the first that far north since 1972. "In most cases,
evidence indicated that locally infected mosquitoes did transmit the
disease," says CDC malaria expert Lawrence Barat, M.D. "Anopheles
mosquitoes are present throughout the contiguous United States. But
we've never found an infected mosquito in the United States. More
recently, we've had outbreaks of Plasmodium falciparum malaria, the more
severe form. We want to monitor this very closely."

For several decades after the Second World War, the drug of choice for
malaria treatment and prevention was chloroquine (Aralen and generics).
"The drug was well-tolerated, fast-acting, and cost only 9 cents to cure
a child," says Robert Gwadz, Ph.D., assistant chief, Laboratory of
Parasitic Diseases, National Institute of Allergy and Infectious
Diseases (NIAID). However, in the 1950s, he says, resistance to
chloroquine in falciparum malaria appeared in South America and
Southeast Asia and spread throughout both continents and eventually into
Africa. "Chloroquine is now useless in most malarious areas."

FDA has since approved numerous anti-malaria drugs. Many are not
marketed here or are used here only for indications other than malaria.

Chloroquine remains the treatment of choice for patients with malaria
caused by species still susceptible to the drug. Resistance to
chloroquine is becoming more common, however, and alternative drugs are
necessary.

In the United States, Barat says, oral quinine given together with
either tetracycline or sulfadoxine-pyrimethamine (Fansidar) is the best
regimen for treatment of mild to moderate falciparum malaria acquired in
areas where resistance to chloroquine has been identified. For patients
with complicated malaria who are too ill to take oral medicine,
intravenous quinidine is used in the United States. Mefloquine (Lariam)
and halofantrine (Halfan) are also used to treat chloroquine-resistant
falciparum malaria. H alofantrine is not currently marketed here.
Intravenous quinine is used in other countries.

The incidence of malaria continues to increase, Gwadz says, "in part due
to the spread of resistance to chloroquine and several of its
substitutes, but also to reduced effectiveness and acceptability of
mosquito-killing insecticides."

In 1995, the World Health Organization established a system to monitor
the drug resistance in Southeast Asia and the Western Pacific.

The parasite can be difficult to treat because it can change form to
escape the human immune system, says Neil Goldman, Ph.D., associate
director for research at FDA's Center for Biologics Evaluation and
Research. Goldman says scientists at the center's Laboratory of
Parasitic Biology and Biochemistry conduct research "to learn how this
process takes place and figure out how to interrupt it. If we make a
break in the circle, maybe we can stop infection."

Gwadz and colleagues are studying how to give mosquitoes a beneficial
gene that prevents transmission of the parasite. To learn more about
mosquito biology, they collaborate with scientists at West Africa's
National School of Medicine and Pharmacy, in Mali.

NIAID scientists also are conducting the first human trial of a vaccine
to block transmission of malaria parasites from infected people.

More from Mosquitoes: Dengue Fever, Yellow Fever 

Aedes mosquitoes, mainly A. aegypti, an urban-dwelling insect, can
transmit four types of dengue viruses, causing about 20 million cases of
disease in more than 100 countries each year. A. aegypti mosquitoes tend
to bite in the daytime, especially just after dawn and just before dark.

Dengue fever begins suddenly with high fever, severe frontal headache,
joint and muscle pain, and sometimes vomiting and rash. Patients usually
recover without complications. More serious, dengue hemorrhagic fever
can lead to shock, bleeding and death. There is no specific treatment.
Symptoms can be treated with bed rest, intravenous fluids, and drugs to
reduce fever.

In 1995, the worst dengue epidemic in 15 years hit Latin America and the
Caribbean. Worldwide, the more than 600,000 cases of hemorrhagic fever
caused 24,000 deaths. CDC in 1995 diagnosed dengue fever in 86 U.S.
travelers, up from 46 during 1993-1994 and 17 in 1992.

A. aegypti mosquitoes also spread the yellow fever virus. Peru in 1995
had the biggest yellow fever epidemic in the Americas since 1950. West
Africa also experienced an epidemic that year.

Mild yellow fever causes flu-like symptoms. Severe cases may involve
bleeding and liver problems, sometimes leading to delirium, convulsions,
coma, and death. Treatment is symptomatic. Prevention consists of
vaccination and personal protection against mosquitoes.

Yellow fever vaccine must be approved by WHO and given at approved
vaccination centers. The Pan American Health Organization (PAHO) helped
in the vaccination campaign that controlled the Peru epidemic. PAHO is
the regional WHO office for the Americas.

Elephantiasis and River Blindness 

Worms related to the heartworms that can hurt dogs, can give humans
lymphatic filariasis, a disease affecting about 120 million people
worldwide. Infected female Aedes, Anopheles, and various other
mosquitoes deposit the worm larvae while biting.

The adult worm can damage the lymph system, resulting in
elephantiasis--disfiguring swelling in the legs, arms, and other areas.
FDA has approved diethylcarbamazine (Hetrazan) for treatment. Surgery
may be needed if certain areas, such as the scrotum, are affected.

River blindness (onchocerciasis) is caused by pre-larval and adult
stages of Onchocerca volvulus, a filarial parasite transmitted by female
black flies. Living near rapidly flowing rivers and streams, black flies
bite by day. Most of the 17.6 million people who have onchocerciasis are
in Africa, though the disease is common in certain areas of Central
America as well. Short-term travelers appear to be at low risk for
infection, which is usually found in Americans only when they stay in
these areas a long time in roles such as missionaries, field scientists,
and Peace Corps volunteers.

Symptoms include an extremely itchy rash, lumps under the skin, and eye
inflammation that can lead to blindness.

Ivermectin kills the parasite at the stage when it causes symptoms.
Merck, Sharp & Dohme provides this drug free to countries where river
blindness is common. It is available here from CDC under an agreement
with FDA. According to John Becher, one of two pharmacists who oversee
the drug service, "We provide certain drugs and biologics as a public
health service. Most are for rare diseases." Ivermectin and other drugs
for tropical diseases available through the service are not approved in
the United States but are provided under investigational drug exemptions
granted by FDA.

NIAID's Laboratory of Parasitic Diseases conducts research toward
vaccines for elephantiasis and river blindness. While nearly everyone
exposed becomes infected, a few individuals are resistant, says Thomas
Nutman, M.D., who heads one immunology section. "These resistant
individuals have antibodies in their blood that are specific to certain
important parasite proteins. We identify the proteins, clone them,
manufacture enough so we can study them, and then test them." Testing is
in test tubes instead of in animals, which don't take the infection as
humans do.

Flatworms, Snails and Schistosomiasis 

Flatworms cause schistosomiasis. First-stage larvae infect freshwater
snails, then evolve into cercariae larvae, which exit the snails and
swim along to find a human host. Penetrating the skin, male and female
cercariae move in the bloodstream to the intestines or bladder and mate.
Eggs excreted in human waste end up in the water supply, restarting the
cycle. About 200 million people worldwide are infected. Severe disease
leads to about 200,000 deaths each year.

Most symptoms are due not to the worms, but to eggs trapped in tissue.
Short-term infection may be symptomless or cause such symptoms as fever,
itchy rash, headache, joint and muscle pain, diarrhea, and nausea.
Chronic infection can damage the liver, kidneys and bladder, or
intestines. FDA has approved praziquantel (Biltricide) as treatment.

Places where schistosomiasis is most prevalent include Brazil, Puerto
Rico, and St. Lucia (an island in the East West Indies); Egypt and most
of sub-Saharan Africa; and Southern China, the Philippines, and
Southeast Asia, according to CDC. At greatest risk are people who wade,
swim or bathe in fresh water in rural areas where sanitation is poor and
snail hosts are present.

Travelers to such areas should not swim in fresh water; salt water like
the ocean and chlorinated pools are considered low risk. Bathing water
should be heated to 50 degrees Celsius (122 degrees Fahrenheit) or
treated with iodine or chlorine, as for drinking. Filtering water with
paper coffee filters may remove the parasites. If these methods are
impossible, CDC recommends that travelers let bathing water stand three
days; cercariae rarely live longer than 48 hours. 

WHO-led researchers are planning to test a vaccine in humans.

Trypanosoma Diseases: Sleeping Sickness, Chagas' Disease 

The parasites Trypanosoma brucei gambiense and T. brucei rhodesiense
cause African sleeping sickness. About 20,000 cases worldwide are
reported yearly. Infected tsetse flies, which bite during the day,
transmit this extremely serious disease.

East Africa's sleeping sickness, due to T. brucei rhodesiense infection,
causes symptoms within days to weeks. West Africa's chronic gambiense
variety may not cause the "sleeping" part of the illness until months to
years after exposure. Symptoms include fever, headache, lethargy, and
confusion, which may progress to convulsions, coma and death. 

Suramin, available from CDC, is for the early stages of both gambiense
and rhodesiense sleeping sickness. Melarsoprol, an arsenic derivative,
is also available from CDC to treat final stages of both varieties. If
the patient is known to have gambiense, however, the drug eflornithine
(Ornidyl), approved by FDA, is more effective and safe because
melarsoprol can cause serious, even fatal, nervous system problems in
some patients. Eflornithine is useful for both early and late stages of
gambiense sleeping sickness; it is not effective for rhodesiense
sickness.

Trypanosoma cruzi causes Chagas' disease, which affects at least 16
million people in Central and South America. The parasite infects
reduviid bugs. When the bugs defecate, they deposit the parasite, which
can enter a human through a break in the skin or through a mucous
membrane, such as that which lines the nose, mouth or eyes. The best
prevention is to avoid potential reduviid habitats--mud, adobe and
thatch buildings, especially those with cracks or crevices. If this
isn't feasible, spraying infested areas and using bed nets can help
prevent infection.

In its short-term stage, Chagas' disease may cause no symptoms or may
cause fever, swollen lymph nodes, and inflammation of the heart or,
rarely, the brain. Deaths occur, mainly in children, but most patients
survive, their symptoms usually disappearing after four to six weeks.
Many years later, about a fourth of patients develop serious, sometimes
fatal, heart infection or damaged digestive organs such as an enlarged
esophagus or colon for the long term. Nifurtimox is available from CDC
for the treatment of short-term Chagas' disease. There is no accepted
anti-parasitic treatment for chronic illness.

About 70 percent of cases occur in Argentina, Bolivia, Brazil, Chile,
Paraguay, and Uruguay. In 1991, the health ministers of those six
countries began a program to eliminate Chagas' disease by the end of
this century. Since then, house infestation has declined 75 to 98
percent in some areas, PAHO reports.


The Leishmaniases 

Sandra Levy is one of an estimated 12 million people worldwide with
leishmaniasis. This group of diseases is spread through the bite of
female sandflies infected with any of about 20 different species of
Leishmania parasites.

Levy had cutaneous leishmaniasis, which causes skin sores that may leave
ugly scars. Mucocutaneous leishmaniasis can cause disfiguring
destruction of membranes in the nose, mouth, or upper throat (pharynx).

In visceral leishmaniasis, parasites invade internal organs, causing
death if the symptoms are untreated. According to the Defense
Department's Magill, "You have chronic fever, depression of bone marrow
and blood cells, weight loss, and a huge spleen so full of parasites it
comes down into the pelvis." Years may pass before symptoms appear.

Recently, 32 Persian Gulf War veterans were identified as leishmaniasis
victims, 12 with viscerotropic leishmaniasis, a chronic syndrome
associated with the infection, Magill says. They had fever and vague
flu-like symptoms, but few signs of overt disease, he says. "Some had
lymph-node enlargement that tended to come and go. A couple had slightly
enlarged spleens."

A free clinical evaluation program has been set up to identify and treat
all veterans infected with leishmaniasis. (See "Want More Information?")

The only current way to confirm a leishmaniasis diagnosis is by finding
parasites in a clinical specimen. FDA is evaluating a skin test
developed by the Defense Department for mass screening of troops.

Preventive measures are staying indoors from dusk to dawn and using bed
nets with 18 or more holes per inch--sandflies are a third the size of
mosquitoes. Treatment of choice is with injectable drugs containing
pentavalent antimony, a potentially toxic metal. "Drugs in this class
remain unapproved by FDA, and no manufacturer has applied for approval,"
says Andrea Meyerhoff, M.D., an infectious disease specialist with the
agency. 

Levy took one such drug, sodium stibogluconate, available on a patient
by patient basis from CDC. Through home care, Levy had an intravenous
dose each day for 20 days.

Although she had a reaction that she describes as "the worst scenario of
flu symptoms," Levy urges those who get leishmaniasis, "Don't think,
'Oh, I'll knock it off.' Go on that medication if it's what your doctor
ordered. It isn't worth taking a chance."

In 1994, FDA designated aminosidine, an antibiotic that does not contain
antimony, as an orphan drug for visceral leishmaniasis, and a sponsor is
working to develop it.

Goldman and colleagues are studying new ways to make a leishmaniasis
vaccine. "We're trying to skew the immune response," he says, "so it
gives a protective reaction to the infection."

Richard Kenney, M.D., a colleague, says, "Past efforts clearly show the
need for a better understanding of the immune response to the parasite."
Toward this end, Kenney and Shyam Sundar, of the Institute of Medical
Sciences, Banaras Hindu University, India, collaborate on studies of the
immune response at various stages of infection and treatment.


The Global Fight Continues 

WHO Director-General Hiroshi Nakajima, M.D., Ph.D., in his message in
the WHO 1996 report, writes that many diseases, including Chagas'
disease and river blindness, "sooner rather than later ... will join
smallpox as diseases of the past." But he also writes that the world is
"on the brink of a global crisis in infectious diseases," requiring "a
global response ... that goes beyond selfish interests and national
boundaries."

Responses by WHO include development of a network of laboratories to
strengthen collaboration in detecting and controlling outbreaks. WHO
teams can be on site within 24 hours with supplies and equipment to set
up epidemic control measures.

The Clinton administration last June established a Presidential Decision
Directive on Emerging Infectious Diseases, including tropical disease,
to improve U.S. and international disease surveillance and prevention
and response measures.

Meanwhile, international travelers can find health advice in CDC's
annually updated handbook, Health Information for International Travel.

As for Levy, her globetrotting has cooled. "My jungle trips are over,"
she says. Her latest trip, last August, was to Iceland.

Dixie Farley is a staff writer for FDA Consumer. Lenore Gelb, a press
officer in the Office of Public Affairs, also contributed to this
article. 

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

Prevention Tips

Personal protection measures are the first line of defense against
tropical diseases. The national Centers for Disease Control and
Prevention advises that international travelers take these steps to
avoid bites from bugs carrying infective organisms:

 * At least six weeks before departure, get current health information
 from CDC on regions you plan to visit. (See "Want More Information?")
 Other sources may be your health department, doctor, or travel agency.

 * Avoiding rural areas when possible may keep you away from some
 disease-causing vectors.

 * When outdoors, wear a hat, long-sleeved shirt tight at the wrists and
 tucked in at the waist, long pants tight at the ankles and tucked into
 socks, and shoes covering the whole foot.

 * On clothing, use a repellent containing permethrin. (Apply it before
 wearing the clothing, and let the clothing thoroughly dry before
 wearing, the Environmental Protection Agency advises.)

 * On skin, use a repellent containing DEET, no higher than 30 percent
 concentration. Follow instructions carefully. There have been
 associated rare cases of toxicity, including deaths.

 * When accommodations are inadequately screened or air-conditioned, use
 a bed net sprayed with permethrin repellent and tucked under the
 mattress. If in an area where Leishmania-infected sandflies are likely
 present, use a bed net with 18 or more holes per inch.

 * Spray screens with permethrin.

 * Use aerosol insecticides to clear rooms of insects. Follow
 instructions carefully.

--D.F. 

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

Want More Information?

 * For health information for international travel, contact CDC's Voice
 or Fax Information Service at (404) 332-4559; World Wide Web site at
 http://www.cdc.gov/; or File Transfer Protocol server at ftp.cdc.gov.

 * Doctors can apply for compassionate use of investigational drugs for
 tropical diseases through the CDC Drug Service by calling (404)
 639-3670.

 * The World Health Report 1996 is available on the World Health
 Organization's World Wide Web site at http://www.who.ch/.

  * Veterans with health-care concerns for themselves, spouses or
 children can call the Department of Defense Persian Gulf Veterans
 Medical Hotline (1-800) 796-9699 or Department of Veterans Affairs at
 (1-800) 749-8387. More details are at VA's electronic bulletin board,
 (1-800) 871-8387; World Wide Web site,
 http://www.va.gov/health/environ/persgulf.htm; and File Transfer
 Protocol/Telnet server, vaonline.va.gov.

--D.F. 


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


Updates

Significant Devices Approved Faster

Faster reviews, significant new products approved, and streamlined
operations highlight FDA's medical device evaluation in fiscal year
1996.

FDA cleared for marketing 4,501 medical devices that were similar to
existing products. This category, called "510(k)" for the section of the
rule governing such devices, covers about 98 percent of all devices sold
in the United States. Average review time was 110 days, down from 137
days in fiscal year 1995 and the peak average of 184 days in fiscal year
1994. In the first three quarters of fiscal year 1996, FDA made
decisions on 93 percent of reviews in 90 days or less, compared with 81
percent in fiscal year 1995.

FDA approved 43 premarket approval applications (PMAs) in fiscal year
1996, 16 more than in fiscal year 1995. Half of these devices are new
technologies for diagnosis and treatment. By contrast, products like
contact lenses, lens care solutions, intraocular lenses, and sutures
made up the bulk of the approvals in the years leading up to 1990. Along
with other streamlining, earlier and more frequent communication with
manufacturers at the clinical study stage enabled this progress.

The agency reviewed eight PMAs in a year or less in fiscal year 1996.
Average review time was 568 days, down from 606 days in fiscal year
1995.

Key PMA approvals in fiscal year 1996 include:

 * the first blood test to monitor patients for possible breast cancer
 recurrence

 * new use of ultrasound to help doctors decide if a breast biopsy is
 needed when a lump is found

 * a spinal fusion implant, the first of its kind, to treat degenerative
 disc disease

 * a fiber-optic bronchial device that uses blue-light wavelengths to
 detect abnormal lung tissue

 * an automated Pap smear scanner to help laboratories detect cervical
 cancer more reliably

 * a system to remove harmful cholesterol from the blood in people who
  have a genetic disorder of extremely high cholesterol levels and are
  at very high risk of heart attack early in life

 * a microwave device to treat symptoms of enlarged prostate

 * the first permanent implant to relieve urinary obstruction in men

 * two lasers that use breakthrough technology to treat nearsightedness

 * a product to help stop urine leakage in women with urinary
 incontinence.

Agency changes in fiscal year 1996 to speed and otherwise improve review
include:

 * Third-party review--This pilot program allows third-party review of
 certain 510(k) devices to test whether private evaluation will save
 time. So far, seven organizations qualify to review.

 * Exemption of 125 types of low- and medium-risk devices from premarket
 notification--This frees FDA time for review of more critical,
 life-saving products.

 * Orphan device program--The program fosters development of devices for
 rare, or "orphan," diseases--those affecting fewer than 4,000 people
 annually. It does not require extensive clinical studies to establish
 effectiveness, provided manufacturers show their products are safe and
 have a probable benefit.

 * Faster review of applications for exemption to study investigational
 devices--More than 70 percent of these applications were approved
 within 30 days.

 * Fewer overdue PMA supplements--Only 17, down from 49 in fiscal year
 1995 and the peak of 173 in fiscal year 1993.

 * Testing faster review of PMA supplements--Pilot-testing of "real
 time" (two weeks or less) review of PMA supplements reduced some times
 to only five days.

 * Testing fewer inspection requirements--FDA pilot-tested a program to
 reduce inspection requirements when manufacturers of new,
 investigational devices change manufacturing sites.

New Drug Approved for Interstitial Cystitis

The first oral medication to relieve the pain and discomfort of
interstitial cystitis (IC), an inflammatory disease of the bladder wall,
has been approved by FDA.

The agency approved the drug, Elmiron (pentosan polysulfate sodium),
last Sept. 26 under its orphan products program, which encourages
development of treatments for rare diseases.

About 450,000 people in the United States are believed to have IC. But
true numbers are hard to come by, because many cases are either
undiagnosed or misdiagnosed. While most cases are in women, at least 10
percent of cases are in men.

No one knows what causes IC. Although bacteria, fungi or viruses are not
found in patients' urine, many researchers believe the cause may be an
infectious agent that hasn't yet been identified. Another theory holds
that the inner lining that protects the bladder wall from toxic effects
of urine may be "leaky," allowing substances in the urine to penetrate
the wall and trigger IC symptoms.

In clinical studies, at least 38 percent of IC patients responded to
treatment with the new drug. How Elmiron relieves the bladder pain
associated with IC is not known, but the hypothesis is that the drug
improves the bladder's defective lining.

Some patients see results in weeks. A few patients may take as long as
six months before getting relief. If pain is not relieved in six months,
the benefits of continuing treatment are unknown.

Elmiron is a weak blood thinner; therefore, patients should tell their
doctors if they are taking other drugs with a similar effect, such as
anticoagulants, or high doses of aspirin or other anti-inflammatory
drugs, such as ibuprofen. A package insert for patients includes
information on side effects, how to take the drug, and who should take
it.

IC symptoms are similar to those of a urinary tract infection. Most
people have some of the following symptoms:

 * urgent need for frequent urination both day and night

 * reduced bladder capacity

 * feelings of pressure, pain and tenderness around the bladder, pelvic
 and genital area, which may increase as the bladder fills and decrease
 as it empties

 * painful sexual intercourse

 * in men, discomfort or pain in the prostatic area.

Elmiron is marketed by Baker Norton Pharmaceuticals Inc., Miami, Fla. At
FDA's request, the firm will conduct postmarketing studies.

(For more information, see "Interstitial Cystitis: Progress Against
Disabling Bladder Condition" in the November 1995 FDA Consumer.)


Breath Test for Ulcer Bacterium

A simple, new breath test--the first of its kind cleared by FDA--is as
good as biopsy in detecting the bacterium associated with the
development of peptic ulcers in people who have developed such ulcers.

The Meretek UBT Breath Test Collection Kit accurately detects H. pylori
bacterium, a common bacterium thought to infect the stomachs of 35
percent of American adults, about 10 percent of whom develop peptic
ulcers. The test is administered in doctors' offices.

Previously, the only accurate way to diagnose H. pylori infection was by
endoscopy with stomach biopsy. In this procedure, the patient is
sedated, and a tube is inserted into the mouth and down into the
stomach, where a sample of stomach lining is removed for analysis. Blood
tests also have been used to detect H. pylori, but with less dependable
results.

With the breath test, the patient drinks a new nonradioactive diagnostic
drug solution and then exhales into the collection kit--all within about
30 minutes. The solution contains the drug Pranactin, which determines
the presence or absence of active H. pylori infection. The collection
kit is sent to the product's manufacturer, Meretek Diagnostics Inc., of
Nashville, Tenn., and results are available within two days.

In studies of 499 U.S. and Canadian patients with duodenal ulcer, the
breath test detected H. pylori in 95 percent of cases confirmed by
biopsy.


FDA cleared the test for marketing Sept. 17, 1996.

(See also "Surprise Cause of Gastritis Revolutionizes Ulcer Treatment"
in the December 1994 FDA Consumer.)


Mammography Info on Internet

Women can now turn to FDA's web site on the Internet to find the nearest
certified mammography facility. Facilities are listed by state and
include the name, address, and phone number. FDA updates the list
periodically to reflect the most up-to-date information.

High-quality mammography is currently the most effective technique for
early detection of breast cancer. Because of concerns about variations
in mammography quality, Congress passed the Mammography Quality
Standards Act in 1992, requiring certification and annual inspection of
mammography facilities. To be certified, facilities must meet quality
standards for x-ray images, equipment and personnel.

(See "Mammography Facilities Must Meet Quality Standards" in the March
1994 FDA Consumer.)


Antimicrobial Drugs
Related to Tendon Problems

At FDA's request, makers of fluoroquinolone antimicrobial drugs are
adding warnings to the package inserts about possible tendinitis and
tendon rupture.

Fluoroquinolones are used to treat bladder, respiratory and other
infections. Under the precautions section in the inserts, the following
information for patients is being added: "Patients should be advised to
discontinue treatment and inform their physician if they experience
pain, inflammation, or rupture of a tendon, and to rest and refrain from
exercise." Another warning will alert doctors to the risk. It states
that ruptures of the shoulder, hand, and Achilles tendons have been
reported and that they r equired surgery or led to prolonged disability.

The affected drugs include Cipro (ciprofloxacin), Penetrex (enoxacin),
Maxaquin (lomefloxacin), Noroxin (norloxacin), and Floxin (ofloxacin).
Tendon rupture can occur during or after therapy with the drugs.


New Law for Animal Drugs

A new law that lends flexibility to the way FDA regulates animal drugs
and medicated feeds is designed to increase the number of animal drugs
without compromising the agency's mission to protect the public health.

The Animal Drug Availability Act (H.R. 2508), supported by FDA's Center
for Veterinary Medicine and animal industry groups, amends the Federal
Food, Drug, and Cosmetic Act to:

 * Allow for more flexibility in studies required to show a new animal
 drug's effectiveness.

 * Provide for greater interaction between drug sponsors and FDA during
 drug development. The law requires a presubmission conference to ensure
 a common understanding about the data needed to establish safety and
 effectiveness and the types of studies needed to provide the data.

 * Create a new category of drugs, Veterinary Feeds Directive Drugs,
 that allows approval and use of sophisticated new animal drugs in feed,
 we incorporating safeguards to ensure the drugs' safe use.

 * Provide for flexible labeling that permits a range of acceptable or
 recommended doses on animal drug labeling, rather than one optimum
 dose.

The new law also directs FDA to propose other changes that would, for
example, broaden the approval process to make more animal drugs
available to treat minor species.

President Clinton signed the law Oct. 9, 1996.


Free Pubs

An FDA Consumer reprint about health information on the Internet and a
low-literacy brochure in Spanish about choosing medical treatments are
available free from FDA. Their titles and publication numbers are:

 * Health Information On-Line (FDA) 96-1253
 * Sea Cuidadoso Al Escoger Los Tratamientos Medicos (FDA) 96-1248S.

To order single copies, 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

Oral Rehydration for Children

This letter pertains to an article entitled "Preventing Dehydration in
Children" that was printed in the July-August 1996 FDA Consumer. The
article provided an informative discussion of the benefits of oral
rehydration therapy (ORT) in the management of diarrhea in children.
However, the following statement included in the article on page 22
inaccurately conveyed that oral rehydration fluids are provided by the
Special Supplemental Nutrition Program for Women, Infants, and Children
(WIC):

"To help with that expense, the federally funded and state-administered
WIC Program pays for ORT along with certain foods for pregnant women,
new mothers, and children under 5."

WIC-eligible formulas issued to program participants include products
classified by FDA as infant formulas and exempt infant foods. The Food
and Consumer Service (FCS), Department of Agriculture (USDA), also
recognizes as WIC-eligible formulas enteral medical foods that are
formulated to provide nutrition support for individuals with a diagnosed
medical condition, when the use of conventional foods is not possible,
inappropriate or inadequate.

A WIC-eligible formula may be either nutritionally complete or
incomplete, but it must serve the purpose of a food, provide a source of
calories and one or more nutrients, and be intended for enteral
digestion via an oral and/or tube feeding. All WIC-eligible exempt
infant formulas and medical foods must be prescribed by a medical
authority for a documented and warranted nutritional need.

As stated in the subject article, ORT fluids (e.g., Pedialyte, Infalyte,
Naturalyte, and Rehydralyte) are intended for very short-term use
primarily with infants or children to replace water and electrolytes
lost during severe bouts of vomiting and diarrhea. An ORT fluid does not
serve the same purpose as a food; therefore, it is not a WIC-eligible
formula. In addition, an ORT fluid does not meet the definition of any
of the other WIC foods.

FCS administers the WIC Program at the federal level. Any questions
about the WIC eligibility of ORT fluids can be directed to my division
under FCS at the address cited below:

Stanley C. Garnett, director
Supplemental Food Programs Division
Food and Consumer Service
U.S. Department of Agriculture
3101 Park Center Drive, Room 540
Alexandria, VA 22302-1500

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


Notebook

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

Over-the-counter drug products containing silver-based ingredients are
not generally recognized as safe and are misbranded, according to an FDA
proposed rule. Many of these products are marketed for treating serious
diseases such as AIDS, cancer, tuberculosis, and malaria. But the agency
is not aware of scientific evidence that supports silver-based
ingredients as disease treatment. Written comments on the proposed rule
must be submitted by Jan. 13, 1997, to the Dockets Management Branch
(HFA-305), FDA, Roo m 1-23, 12420 Parklawn Drive, Rockville, MD 20857.
(FR Oct. 15)

A report on conjugated estrogens, used for estrogen replacement in
women, is available free from FDA. The agency recently sought public
comment on its preliminary analysis of the Premarin brand of conjugated
estrogens to help decide which components should be included in the
generic version of Premarin. "Preliminary Analysis of Scientific Data on
the Composition of Conjugated Estrogens" (a 692k PDF file) is available
on the World Wide Web at http://www.fda.gov/cder/; the document is also
available through " fax on demand" at (1-800) 342-2722.

Conditions in cattle such as gastrointestinal roundworms, lungworms,
eyeworms, grubs, lice, and mange mites may be treated with Dectomax
(doramectin) 1% solution, says an FDA final rule. Cattle are not to be
slaughtered within 35 days of treatment, and the product is not for use
in dairy calves 20 months or older or in calves to be processed for
veal. (FR Oct. 11)

A genetically engineered mouse that should boost understanding of
Alzheimer's disease and ultimately allow for testing of drug therapies
has been developed by University of Minnesota researchers. The mouse is
the first to exhibit both behavioral characteristics of Alzheimer's
dementia and protein-derived plaques like those in the brains of people
with the disease. (Science, Oct. 4)

Children's test scores appear to improve when youngsters eat breakfast
close to test time, according to Israeli research. A study examined 569
children, aged 11 to 13, of varying socioeconomic backgrounds. While
eating breakfast two hours before a test did not appear to improve the
children's cognitive functions, test scores improved significantly when
children ate breakfast just half an hour before a test. (Archives of
Pediatrics and Adolescent Medicine, October 1996)

Depression may increase a woman's risk for broken bones, suggests a
National Institute of Mental Health study. Researchers found the hip
bone density of women with a history of depression to be 10 to 15
percent lower than normal for their age--so low that their risk of hip
fracture increased by 40 percent over 10 years. Excess cortisol
secretion, a common feature of some forms of depression, is known to
cause bone loss and could account for some of the observed deficits, the
researchers say. (New England Journal of Medicine, Oct. 17)


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

Investigators' Reports


Fast-Forwarding Video Service Permanently Ejected

by Isadora Stehlin 

"Capture the joy of your unborn baby on videotape."

Through the use of modern ultrasound, a Georgia company offered
expectant parents this special service to add to their video library.

But FDA says these "keepsake videos," taken for purely entertainment
purposes without a doctor's prescription and for no medical reason, are
an unapproved use of ultrasound equipment and therefore illegal. As a
result, in the first such action of its kind, Fetal Fotos of
Gainesville, Ga., agreed in a consent decree signed Sept. 12 to stop
producing ultrasound images of unborn babies without a written
prescription from a licensed doctor.

According to Tom Jakub, chief of the diagnostic devices compliance
branch in FDA's Center for Devices and Radiological Health,
obstetricians use ultrasound imaging to check the size, location,
number, or age of fetuses; the presence of some types of birth defects;
and fetal movement, breathing and heartbeat. "Ultrasound is generally
considered safe when properly used for medical reasons, and often the
doctor will give parents a still photo from these tests," he says.

But Fetal Fotos did not provide a medical service, as Fulton Varner and
Andrew Paeng, investigators with FDA's Atlanta district office, learned
when they first inspected Fetal Fotos on May 24, 1995. The inspection
was part of FDA's nationwide effort to identify companies using
ultrasound for unapproved uses. They questioned Donna Jans, owner of
Fetal Fotos and a registered diagnostic medical sonographer, who
admitted using an ultrasound scanner system to produce keepsake videos
for $75.

The investigators also learned from Jans that she gave customers a
consent form that stated "this service is provided only for the purpose
of creating the said videotape ... Fetal Fotos does not provide any
diagnostic service or any service which could in any manner be construed
to be a medical service."

According to Varner, Jans would ask a prospective customer if she had
discussed the procedure with a doctor, but if the customer hadn't, she
still performed the sonography. In addition, the only record she kept of
ultrasound procedures was a customer appointment log.

FDA's Atlanta office sent a warning letter to Fetal Fotos on June 8,
1995, advising the company that this unapproved use of a medical device
caused the device to be adulterated and misbranded. FDA warned the
company to stop the unauthorized use of the device or face possible
regulatory action such as seizure or injunction.

In response to the warning, Jans, through her attorney, told the agency
that Fetal Fotos would not produce any more keepsake videos and would
provide diagnostic imaging only with a "prescription or other order of a
licensed physician."

However, when Paeng returned to Fetal Fotos on March 29, 1996, he found
that Jans was still producing keepsake videos. The investigator
contacted two of the doctors listed in Jans' records as having given
verbal consent for her to perform the procedure on their patients. But
the doctors told Paeng that Jans had never contacted them and that they
had not issued written prescriptions or verbally authorized the
procedure for their patients.

When confronted with this information, Jans admitted that she had never
contacted the doctors and, despite FDA's warning letter and three
inspections, she indicated that she did not intend to change her
business practices.

On April 30, FDA asked the U.S. attorney for the Northern District of
Georgia to file a complaint for seizure. The complaint was filed on June
17, and a U.S. marshal seized the equipment and promotional brochures on
July 8.

In the consent decree signed and entered in the U.S. District Court for
the Northern District of Georgia, Jans agreed to stop producing
ultrasound images of babies still in the womb without a doctor's written
prescription and to keep detailed records of all ultrasound exams
performed, including:

 * written prescriptions
 * names, addresses and phone numbers of prescribing doctors
 * patients' names
 * date and length of exams
 * patients' previous ultrasound exams.

At press time, Jans had resumed business, and the agency planned to
reinspect to make sure she was following the consent decree.

Isadora Stehlin is a member of FDA's public affairs staff. 

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


Bulk Latex Gloves Blamed for Fires

An import alert remains in effect for certain powder-free latex patient
examination gloves imported from China. The gloves have the potential to
spontaneously combust.

The patient examination gloves were imported by a California company and
labeled "Made in China." Fire inspectors attributed three warehouse
fires in 1995 to the gloves. 

FDA issued the import alert in 1995, and, following an investigation,
issued a public health advisory last summer to hospitals, manufacturers
and distributors to inform them that powder-free latex examination
gloves have the potential to ignite when stored in large quantities in
extreme heat.

FDA continues to study the combustibility of imported powder-free latex
examination gloves from China and other countries. According to John
Farnham, a consumer safety officer in FDA's Center for Devices and
Radiological Health, the United States imports 17 million shipments of
latex medical gloves each year.

Powder-free latex gloves are believed to have caused fires in Memphis,
Tenn., Middlesex, N.J., and New York City, in spring and summer 1995. In
the latter, 67 firefighters were injured battling an eight-alarm fire at
Brooklyn Navy Yard. The suspect gloves were imported from China by SJS
Supreme Inc. of Yorba Linda, Calif.

FDA issued the import alert Aug. 7, 1995, calling for all shipments of
powder-free latex examination gloves imported by SJS to be detained at
their ports of entry. On Aug. 18, FDA sent SJS a letter, notifying the
importer that, because of the fires, it would have to "eliminate the
unreasonable risk of substantial harm ... to persons who may be directly
or indirectly exposed to these devices."

SJS recalled the gloves. In a Sept. 18 letter, SJS asked the five
distributors that had received shipments of the gloves to destroy their
SJS powder-free latex examination glove inventory according to local
laws on proper disposal of combustible materials.

That same month, FDA investigators inspected several Chinese latex
examination glove manufacturing facilities and found "numerous GMP [good
manufacturing practice] violations," according to Dan Rowland, a
compliance officer with FDA's Los Angeles district office. FDA officials
also contacted the State Pharmaceutical Administration of China, the
Chinese agency that regulates medical devices in that country.

In early 1996, the Office of Science and Technology in FDA's Center for
Devices and Radiological Health tested the thermal stability of imported
powder-free latex examination gloves by exposing them to heat. The tests
revealed that the SJS-imported gloves produced more heat than that to
which they were exposed, suggesting that the gloves were capable of
spontaneous combustion.

Scientists with FDA's Forensic Chemistry Center in Cincinnati then
compared the heat-producing gloves to non-heating ones and found
chemical differences between the two. The center is now working on a
test to detect gloves that could spontaneously ignite.

FDA's public health advisory, issued June 27, 1996, urged hospitals,
distributors, and other facilities that store large quantities of
powder-free patient examination gloves to take certain precautions to
reduce the risk of the gloves igniting. FDA advised these businesses to
avoid large inventories of powder-free latex examination gloves and to
break apart stacked cartons to allow air to circulate more freely.

FDA's research indicated that higher temperatures short of ignition
could cause latex gloves to deteriorate and lose their effectiveness as
an adequate barrier. So, the agency's health advisory also cautioned
hospitals and distributors to check powder-free latex examination gloves
regularly for brittleness, tackiness, and an acrid chemical odor--all
signs of latex glove deterioration.

According to FDA's Rowland, the agency is working with the U.S. Customs
Service to determine how best to handle one last shipment of the suspect
powder-free gloves detained in Los Angeles.



--Paula Kurtzweil

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


A Case of Ackees
And Other Smuggled Goods

A Rochester, N.Y., wholesale food distributor voluntarily destroyed his
supply of smuggled goods--a potentially poisonous tropical fruit and an
unapproved drug promoted for use in babies. This followed a joint
investigation by FDA, the U.S. Customs Service, and the state of New
York.

The government learned of the goods on Sept. 28, 1995, when an anonymous
source called FDA's Buffalo, N.Y., district import operations branch to
report that the distributor was selling canned ackees, a fruit widely
eaten in Jamaica but banned in the United States.

Under an FDA import alert, ackees are supposed to be detained at U.S.
borders because the fruit contains natural toxins that can cause
illness, even death. The toxins are in the fruit's flesh when the fruit
is either green or overripe and in the seeds of the fruit at all times.
The ackee is conclusively linked to "vomiting sickness" in Jamaica,
causing convulsions, coma and death in most cases.

Mark Prusak, the FDA compliance officer who took the complainant's call,
tried repeatedly to meet with the person to get more information, but
without success. About a month later, he met to discuss the illegal
products with a customs special agent and James Sevchik, chief inspector
with the New York State Department of Agriculture and Markets.

On May 29, 1996, Prusak, the customs agent, and Robert Weinberg, another
state inspector, visited the wholesale food distributor unannounced and
talked to the firm's president.

"We told him why we were there," Prusak says, "and asked him where the
ackees were. He showed us one case." Labels identified the fruit as
packed for Palm Rose Ltd., Kingston, Jamaica.

The president admitted he bought five to 10 cases a month at $105 to
$110 per case, ordering the fruit by telephone from an individual at New
York's Bronx Terminal Market. He had no records of the purchases, he
said, because he always paid in cash, putting it in an envelope and
handing it to a truck driver, who took the payment to the contact at the
market and picked up the ackees and brought them back to the store.

Weinberg embargoed the ackees and ordered the firm to store them until
further action.

As the investigators continued their inspection, Weinberg noted 24
bottles of Woodward's Gripe Water on the store's shelves. He called the
bottles to Prusak's attention. When questioned, the president said he
bought this product from another source in the Bronx.

Woodward's Gripe Water contains dill oil or dill water, sodium
bicarbonate, alcohol, and other substances. Labeled for such medical
uses as relieving baby's hiccups and minor stomach upsets, the product
has been used in a number of other countries for years. In the United
States, however, FDA considers it an unapproved drug. FDA also requires
it to be detained at U.S. borders.

After Prusak informed the distributor that the product was illegal, "he
agreed to destroy the gripe water," Prusak says, "and signed an
affidavit attesting to this." As Prusak and the others watched, the man
opened each bottle and poured the contents down a sink drain.

After being warned by the customs agent against dealing in smuggled
goods, the distributor promised he would no longer handle either the
ackees or the gripe water. In addition, he provided the names and
addresses of his buyers--three grocery stores and three restaurants in
Rochester and two restaurants in Syracuse.

State inspectors made sure the ackees were removed from the grocery
stores. FDA's Buffalo district office notified the agency's New York
district office of the alleged sources of the ackees and gripe water for
follow-up.

On June 7, 1996, under Weinberg's supervision, the distributor destroyed
the embargoed ackees by opening the cans and pouring a denaturing
chemical over the product.



--Dixie Farley 

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

Summaries of Court Actions

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

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



SEIZURE ACTIONS

Food/Contamination, Spoilage, Insanitary Handling

PRODUCT: Mushrooms, at Brooklyn, N.Y. (E.D.N.Y.); Civil Action No.
CV-95-0324.

CHARGED 1-23-95: While held for sale after shipment in interstate
commerce at Good World Trading Co., in Brooklyn, N.Y., the articles were
adulterated in that they contained an added poisonous and deleterious
substance which might render them injurious to health--402(a)(1). The
articles were also adulterated in that they were prepared and packed
under conditions whereby they might have been rendered injurious to
health--402(a)(4). The articles were misbranded in that their labeling
falsely represented that they were grown and packed in Taiwan and that
they were sliced mushrooms--403(a)(1).

DISPOSITION: A decree of forfeiture and order of final delivery ordered
the articles destroyed. (F.D.C. No. 67040; S. No. 94-725-854; S.J. No.
1)



Drugs/Human Use

PRODUCT: IKB gel, at Miami Lakes, Fla. (S.D. Fla.); Civil Action No.
96-1281-CIV-KING.

CHARGED 5-13-96: While held for sale after shipment in interstate
commerce at Tex International, Inc., in Miami Lakes, Fla., the articles
were adulterated in that their strength differs from and their quality
falls below that which they were represented to possess--501(c). The
articles were misbranded in that their labeling falsely represented that
they contained halcinonide and neomycin sulfate, and the information
required to appear on the label did not appear in the English
language--502(a) and 502(c). The articles were also misbranded in that
they were not duly listed as required, and their labeling failed to bear
the statement "Caution: Federal law prohibits dispensing without a
prescription."--502(o) and 503(b)(4).

DISPOSITION: The articles were destroyed. (F.D.C. No. 67141; S. No.
96-711-338; S.J. No. 2)





Medical Devices

PRODUCT: Dilapan hygroscopic cervical dilators, at Middlesex, N.J.
(DNJ); Civil Action No. 92-1894(DRD).

CHARGED 5-7-92: While held for sale after shipment in interstate
commerce at Gynotech, Inc., in Middlesex, N.J., the articles were
adulterated in that they were class III devices without an application
for premarket approval--501(f)(1)(B). The articles were also adulterated
in that the methods used in, and the facilities and controls used for,
their manufacture, packing and storage were not in conformity with
current good manufacturing practice requirements--501(h). The articles
were misbranded in that their labeling failed to bear adequate
directions for use, and the information required to be submitted to the
agency was not submitted--502(f)(1) and 502(t)(2).

DISPOSITION: The court enjoined the firm and its owner from distributing
the articles in interstate commerce. Subsequently, an inspection of the
firm revealed that it had ceased manufacturing and distributing the
articles. (F.D.C. No. 66325; S. No. 91-612-926; S.J. No. 3)


PRODUCT: Synchro tech relaxman, at Cleveland, Ohio (N.D. Ohio); Civil
Action No. 1:93CV1577.

CHARGED 7-28-93: While held for sale after shipment in interstate
commerce at Meta Brain/Mind Biomedical Research Foundation in Cleveland,
Ohio, the article was adulterated in that it was a class III device
without an application for premarket approval--501(f)(1)(B). The article
was misbranded in that its labeling falsely represented that it was
adequate and effective for pain reduction, efficient digestion, waste
elimination, better sexual functioning, and healthful physical energy
levels--502(a). The article's labeling failed to bear adequate
directions for use, and it lacked adequate warnings against use in those
pathological conditions where its use might be dangerous to
health--502(f)(1) and 502(f)(2). The article was also misbranded in that
its use is a danger to health when used in the dosage or manner and with
the frequency suggested on the labeling, and notice was not provided to
the agency prior to the article's release into interstate
commerce--502(j) and 502(o).

DISPOSITION: The article was destroyed. (F.D.C. No. 66662; S. No.
93-670-602; S.J. No. 4)



CRIMINAL ACTIONS


DEFENDANT: W.W. Hurt d/b/a New River Livestock Company, at Blacksburg,
Va. (W.D. Va.); Criminal No. 93-00122.

CHARGED 7-23-93: Count 1: The defendant willfully conspired to defraud
FDA by impeding its efforts to prevent adulterated meat intended for
human consumption from entering interstate commerce and to defraud the
Packers and Stockyards Administration (PSA) by impeding its efforts to
ensure fair practices among livestock dealers and to protect consumers
and members of the livestock and meat industries--18 U.S.C. sections 371
and 2. The defendant also devised a scheme using the telephone to
defraud FDA and PSA- -18 U.S.C. section 1343. Count 2: The defendant,
with the intent to defraud, willfully conspired to introduce into
interstate commerce adulterated food which contained unsafe new animal
drugs--18 U.S.C. sections 371 and 2. Count 3: The defendant, with the
intent to defraud, delivered to slaughterhouses for slaughter and human
consumption cows whose tissues contained unsafe new animal drugs--301(a)
and 303(a)(2). Count 4: The defendant delivered cows to a slaughterhouse
that were infected with a poisonous and deleterious substance that might
render the food injurious to health--301(a) and 303(a)(2). Count 5: The
defendant knowingly made a false statement to an FDA investigator that
he was employed as a truck driver by the New River Livestock Company
(NRLC) when, in fact, he controlled NRLC--18 U.S.C. section 1001. Count
6: The defendant knowingly made a false statement to an investigator
that he did not ask producers whether animals were medicated, when, in
fact, he frequently asked producers for this information--18 U.S.C.
section 1001. Count 7: The defendant, for purposes of executing the
scheme to defraud, used the telephone to conduct the business of NRLC by
placing calls and receiving telephone wire communications from other
cattle farmers and producers regarding the availability of cows for
sale, and for making arrangements for transporting and purchasing these
cows--18 U.S.C. section 1343.

DISPOSITION: The defendant pleaded guilty to count three. He was
sentenced to six months of imprisonment and 12 months of supervised
release. He was also ordered to pay a $2,500 fine and a $50 assessment.
(F.D.C. No. 66105; S. No. 91-662-441; S.J. No. 5)



INJUNCTION ACTIONS

DEFENDANTS: Roy H. Bowersox, at Winfield, Pa. (M.D. Pa.); Civil Action
No. 1:CV-93-0545.

CHARGED 4-13-93: The defendant delivered into interstate commerce
adulterated cattle--301(a). The cattle were adulterated in that they
contained an unsafe new animal drug--402(a)(2)(D).

DISPOSITION: A consent decree of permanent injunction was filed. A
follow-up inspection revealed the defendant had not changed operating
practices. Subsequently, Mr. Bowersox attested that he no longer sells
or delivers cows, and he intended to refrain from doing so in the
future. (Inj. No. 1295; S. No. 92-632-209; S.J. No. 6)


DEFENDANTS: Novie Iceland and Barry Karch, at Miami, Fla. (S.D. Fla.);
Civil Action No. 95-1005.

CHARGED 5-15-95: The defendants introduced into interstate commerce
adulterated ready-to-eat smoked and unsmoked fish products. The fish
products were adulterated in that they were prepared, packed or held
under insanitary conditions whereby they might have become contaminated
with filth--402(a)(4).

DISPOSITION: The firm filed for Chapter 11 under the U.S. Bankruptcy
Code. Subsequently, the bankruptcy case was converted to a Chapter 7
liquidation. (Inj. No. 1368; S. No. 91-594-341; S.J. No. 7)





MISCELLANEOUS ACTIONS

ACTION: Kimball v. Clausnitzer, et al., at Tampa, Fla. (M.D. Fla.);
Civil Action No. 95-1399-Civ-T-24E.

CHARGED 8-23-95: The plaintiff alleged that various federal officials
deprived him of his fourth, fifth, ninth, and 14th Amendment rights. The
allegations arose from an FDA investigation into the manufacture and
distribution of unapproved cancer and AIDS drugs.

DISPOSITION: The court found that the plaintiff failed to state any
constitutionally based claim upon which relief could be granted. The
court gave the plaintiff 11 days to amend the complaint. Subsequently,
the court denied the plaintiff's motion for leave to amend the complaint
and add parties. The court also granted a defendant's motion for award
of attorney's fees and costs. (Misc. No. 1111; S.J. No. 8) 

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

FDA Consumer is the official magazine of the U.S. Food and Drug
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
products.

FDA Consumer is published monthly, except for combined issues for
July-August and January-February. Subscriptions are available for $15
per year by writing:

Superintendent of Documents
Government Printing Office
Washington, DC 20402-9371.

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