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stimulus transmitted by the nervous system,' Sweeney explains. "Normal cardiac
muscle knows how to activate itself. The heart's pacemaker distributes the
electrical stimulus to keep it beating in a natural rhythm"
Of course, skeletal muscle is designed for different purposes as well. But
Sweeney and other researchers are devising functional neuromuscular
stimulation (FNS) systems that might be used to artificially convert skel-etal
muscle into tissue that could help the heart pump {*filter*}.
"Two approaches are being discussed,' Sweeney says. "The first is
cardiomyoplasty. The second approach is probably a bit further down the road.
The idea is to actually build a small heart out of skeletal muscle. Called a
skeletal muscle ventricle, this new heart would work in parallel to assist the
natural heart"
From the engineer's viewpoint, the most elegant and efficient solution for
creating an artificial device that can temporarily replace the heart would be
to build a pump that is powered by the body itself, Guilbeau says. Instead of
an electrical power source, all that would be needed is a cooking.net">food source.
"There are some challenges with bio-compatibility" he says. "But they are
being met. The task is to couple living tissue with a mechanical device or
with other types of living tissue in such a way that the coupling doesn't
fail. The body helps because of its re-markable ability to adapt to adverse
situations"
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Volume 6, Number 8 April 4, 1993
To be effective, Sweeney says that both cardiomyoplasty and the skeletal
muscle ventricle approach will require some type of control mechanism, a type
of "pacemaker technology"
"The implantable heart pacemaker often is called the 'grandfather of FNS
systems.' Pacemakers are the most successful applica-tion of electrical
technology for controlling muscle,' he says.
Assisted by graduate student Bob De Luca, Sweeney's immediate interest is in
devel-oping a stimulation scheme that will make skeletal muscle contract in a
controllable sequence. Heart muscle contracts in an undulating cascade,
rippling across cells at one end of the muscle to the other. The result is an
effective squeezing action that pumps oxygen-rich {*filter*} through the heart's
chambers with enough pressure to send it coursing through the miles of
arteries and capillaries to every cell in the body.
"We want to emulate that contraction cycle in latissimus dorsi muscle by using
a particu-lar type of stimulation scheme,' Sweeney explains. "No one can do
this at present. But most of the work to date has been clinical in nature. I'm
e{*filter*}d about approaching it from the bioengineering perspective"
Guilbeau and Sweeney both agree that this area of research holds intuitive
appeal for sci-entists. Possibilities for success seem abundant with very few
apparent stumbling blocks.
"Artificial organs require an external power source. But skeletal muscle runs
off the body's own energy supply. That is one big advantage" Sweeney says.
"Although skeletal muscle must be transplanted, it comes from the same body,
which alleviates the chance of rejection. And we now know that skeletal muscle
can be converted electrically to work like heart muscle"
All is not perfect, of course. Using either of these procedures will require
the surgeon to take muscle from one portion of the body to assist the heart.
"For example, if a portion of the latissimus dorsi is used, then the patient
will lose full use of that muscle. We'll be trading his or her ability to do
chin-ups or certain swimming strokes in order to repair the heart"
The compromise would appear to be quite acceptable to people who are very sick
in the first place. Most would rather live than swim laps or do chin-ups.
Health InfoCom Network News Page 43
Volume 6, Number 8 April 4, 1993
::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
Announcements of Studies/Research
::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
NIAID Begins First Test of Novel HIV Peptide Vaccine
***********************************************
National Institutes of Heath
National Institute of Allergy and Infectious Diseases
February 12, 1993
The National Institute of Allergy and Infectious Diseases (NIAID) has
begun the first human trials of an experimental vaccine containing several
copies of a chemically synthesized protein fragment, or peptide, of HIV, the
virus that causes AIDS.
The Phase I trial will examine the product's safety and immune-
stimulating ability in 36 uninfected men and women at low risk of HIV
infection. Volunteers between the ages of 18 and 60 are being recruited in
St. Louis, Mo., and Rochester, N.Y., through NIAID's AIDS Vaccine Clinical
Trials Network, says study coordinator Geoffrey Gorse, M.D., of the St. Louis
University School of Medicine.
"Peptide vaccines have two particular strengths: they are inexpensive
and relatively easy to modify," comments Margaret I. Johnston, acting deputy
director of NIAID's Division of AIDS (DAIDS), "to include new mixtures of
peptides and those from different HIV strains." With such flexibility, Dr.
Johnston says, peptide vaccines have the potential to stimulate a broad range
of immune responses to accommodate significant changes in the virus as they
occur.
Recent studies indicate that HIV strains now fall into at least five
genetically distinguishable groups. Scientists have expressed concern that
protection in one individual over time or of people in different countries may
be difficult to achieve with a vaccine made from a single virus strain, says
Patricia Fast, M.D., who heads the HIV vaccine clinical trials effort in
DAIDS.
The prototype vaccine incorporates eight copies of one peptide from
the MN strain, representative of a common U.S. strain. The vaccine
manufacturer, United Biomedical, Inc. (UBI), of Hauppauge, N.Y., eventually
wants to develop a multicomponent vaccine incorporating a mixture of peptides
capable of providing protection against worldwide strains of HIV.
The peptide used in the vaccine lies on the surface of HIV in an area
known as the V3 loop. Scientists have identified the V3 loop as a primary
site that stimulates immune reactions to the virus.
Almost all candidate vaccines in NIAID-sponsored trials so far have
been subunit vaccines--genetically engineered proteins of HIV such as gp120 or
gp160--made from single HIV strains. UBI's vaccine is the eighth product and
first peptide vaccine studied by NIAID's network, and one of several novel HIV
Health InfoCom Network News Page 44
Volume 6, Number 8 April 4, 1993
vaccines expected to enter NIAID trials this year.
The NIAID trial will evaluate three doses of the vaccine. For each
dose, 10 volunteers will be chosen at random to receive the vaccine containing
alum adjuvant, a substance that boosts specific immune responses. Two
volunteers will receive a placebo, alum alone. Neither the participants nor
the health care workers will know who gets the vaccine. Each volunteer will
receive a primary injection into the muscle and booster shots one and six
months later. Dr. Gorse and his colleagues will immunize volunteers with the
low-dose vaccine first and move to the next higher dose only after determining
that the lower dose is safe.
For more information about the trial, call the AIDS Clinical Trials
Information Service at 1-800-TRIALS-A, open weekdays 9:00 a.m. to 7:00 p.m.
EST, or the individual units at the numbers listed below.
St. Louis University School of Medicine
St. Louis, Missouri
Geoffrey Gorse, M.D./Robert Belshe, M.D.
Contact: Carol Berry (314) 577-8649
University of Rochester Medical Center
Rochester, New York
Michael Keefer, M.D./Raphael Dolin, M.D.
contact: Shirley Erb (716) 275-5871
Health InfoCom Network News Page 45
Volume 6, Number 8 April 4, 1993
::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
AIDS News Summaries
::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
AIDS Daily Summary for March 29 to April 2, 1993
The Centers for Disease Control and Prevention (CDC) National AIDS
Clearinghouse makes available the following information as a public service
only. Providing this information does not constitute endor{*filter*}t by the CDC,
the CDC Clearinghouse, or any other organization. Reproduction of this text
is encouraged; however, copies may not be sold. Copyright 1993, Information,
Inc., Bethesda, MD
====================================================================
March 30, 1993
====================================================================
"NIH Starts Safety Trials of HIV Vaccine for Young" Wall Street Journal
(03/30/93), P. B6
The National Institutes of Health has announced that it has initiated
the first trial of AIDS vaccines in HIV-positive children. The safety trial
is intended to determine whether a therapeutic vaccine can postpone the onset
of AIDS in HIV-infected children. The children involved in the clinical
trial will be aged one month to 12 years. The vaccines are manufactured by
Chiron Corp.'s Biocine joint venture with Ciba-Geigy, in Emeryville, Calif.;
Genentech Inc. of South San Francisco, Calif.; and MicroGeneSys Inc. of
Meriden, Conn. Secretary of Health and Human Services, Donna Shalala, said
the study is "a hopeful milestone in our efforts to ameliorate the tragedy
of HIV-infected children who now face the certainty that they will develop
AIDS." In a separate issue, the NIH has verified that MicroGeneSys has
withdrawn from a similar three-way therapeutic vaccine trial in {*filter*}s, as a
result of a disagreement over study design. Last fall, the company spurred
controversy by lobbying Congress to appropriate $20 million for a Defense
Department study of its product alone. Related Story: USA Today (03/30) P.
1D
====================================================================
"Health and Behavior: HIV, Immigration, and Rise in Tuberculosis" USA Today
(03/30/93), P. 4D
Federal health officials said Monday that the growing number of HIV-
positive patients and infected immigrants have contributed to the re-emergence
of tuberculosis in the United States. In the mid-1980s, the prevalence of TB
had declined to record lows. However, in 1991, there were 26,283 new cases,
Health InfoCom Network News Page 46
Volume 6, Number 8 April 4, 1993
which is 18 percent higher than 1984. Dr. Anthony Fauci of the National
Institutes of Health told a U.S. House subcommittee Monday that TB
transmission often transpires in hospitals, prisons, and shelters, where
those infected with HIV comprise an increasing population. Dr. William
Roper, outgoing director of the Centers for Disease Control, cited several
other groups also at high risk including: immigrants from countries with high
rates of TB, elderly nursing home residents, children under five years of
age, and the poor.
====================================================================
"Researchers at UC San Francisco and The Gladstone Institute Map Key Protein
Interaction Believed to Control HIV Growth Inside Cell" Business Wire
(03/25/93)
San Francisco--The direction of a cellular protein interaction which
plays a key role in controlling the growth of HIV inside human T-cells has
been tracked by University of California-San Francisco researchers at the
Gladstone Institute of Virology and Immunology. The proteins, called NF-
Kappa-B and I-Kappa-B, are inactive when the T-cell is in a resting state.
However, once an HIV-positive T-cell is activated, these proteins incite the
series of events that leads to reproduction of the virus inside the cell
nucleus, the researchers report in the March 26 issue of Science. The
scientists also found a unique relationship between the proteins, in which NF-
Kappa-B is initially inhibited by I-Kappa-B but is released and later spurs
new production of its own inhibitor. Warner C. Greene, M.D., Ph.D., UCSF
professor of medicine, microbiology, and immunology, and chief author of the
report, said I-Kappa-B's normal function is to help regulate cell growth and
monitor how the cell responds to all kinds of outside invaders, such as
bacteria and viruses. As a result of understanding the inner workings of
HIV, researchers may reveal new ways to block the virus' destructive path.
Researchers in Greene's lab monitored the action of I-Kappa-B over a few
hours, noting its presence, disappearance, and then re-emergence inside an
activated human T-cell. The researchers discovered that the protein
initially serves as an anchor for NF-Kappa-B, which normally sits outside the
nucleus of the cell. When the cell is subjected to an outside offender, I-
Kappa-B releases its captive NF-Kappa-B, which then moves to the nucleus to
activate genes which help fight off the invader.
====================================================================
"CDC-TB" Associated Press (03/25/93)
Atlanta--Federal health officials announced Thursday that more than
200,000 people released from prisons and drug-treatment centers may spread
tuberculosis every year if those institutions don't test and treat every one
who enters the facilities. Christopher Hayden of the Centers for Disease
Control conceded that attempting to get prisoners and clinic patients "to
Health InfoCom Network News Page 47
Volume 6, Number 8 April 4, 1993
complete a full, uninterrupted course of preventive therapy unless they are
in a supervised setting would be almost impossible. About 10 million
Americans are carriers of TB, and about 20,000 active cases are diagnosed
each year. However, the prevalence of TB is three times higher in prisons
than the general population. It is also high at drug-treatment centers
because drug users and HIV-positive patients are most at risk. HIV-positive
patients with TB must receive 12 months of medication, while HIV-negative
patients must receive only six months. The CDC said that every year, 540,000
inmates are released and 645,000 people finish treatment at drug clinics.
Also, about 240,000 of them have latent TB infection and spread the germ.
The federal agency issued the first concrete evidence that those facilities
not only are important test sites, but also can succeed in helping those at
high risk for TB to complete treatment and prevent the spread of disease.
Nevertheless, the American Correctional Health Services Association told the
CDC two weeks ago that most prisons cannot afford to even test for TB, much
less provide preventive treatment. Hayden said that the CDC funded TB
programs at 25 prisons and drug clinics in 1990 and 1991 and has added
another 13 prisons and clinic TB programs to the list this year.
====================================================================
"How Clean Needles Are Saving Lives" U.S. News & World Report (03/29/93) Vol.
114, No. 12, P. 24 (Friedman, Dorian)
As the debate continues over the distribution of clean needles to IV-drug
users, there is increasing evidence that these programs are preventing new
cases of HIV infection and saving lives. Many conservative politicians and
some religious and black leaders oppose the programs, claiming they promote
drug use. But a study by Yale University researchers started in 1990 has
shown that the share of returned used needles testing positive for HIV has
dropped significantly--from 68 percent to 41 percent. It has also found that
more {*filter*}s are trading in more needles and they are holding on to them a
shorter time, indicating they are sharing them less. Moreover, the Yale
group predicts a reduction of at least 33 percent in the rate of new HIV
infections. The study's findings have prompted similar efforts in the United
States. San Francisco Mayor Frank Jordan declared a public health emergency
last week so his city could implement a successful--but until now, illegal--
needle exchange program despite opposition from some state officials. Also,
in New York City, Mayor David Dinkins moved to legalized needle-exchange
programs last year. The early findings suggest that needle sharing is down,
referrals to drug treatment are increasing, and there is no evidence that the
programs have attracted new drug users. Prof. Edward Kaplan, head of the
Yale research team, said, "All evidence strongly suggests that these programs
can work well. So the idea that they shouldn't even be considered strikes
me as very bad public policy." This week, the federal General Accounting
Office is expected to reinforce the positive findings in a review.
Health InfoCom Network News Page 48
Volume 6, Number 8 April 4, 1993
===========================================================================
March 31, 1993
===========================================================================
"Free Trial Offer for New AIDS Drug" Business Ethics (03/93-04/93) Vol. 7, No.
2, P. 9
Vestar Inc., a San Dimas, Calif., pharmaceutical company will soon
launch a clinical trial of a new AIDS drug, DuanoXome, that will be given to
patients free of charge. Michael Hart, Vestar's executive vice president and
chief financial officer, said, "Some of the more advanced clinical trials have
very specific requirements. This one, however, was set up in response to the
interest AIDS groups have shown in the drug. We wanted to allow a wide range
of patients access to the drug before it becomes officially approved by the
FDA." In earlier trials, more than half of AIDS patients with advanced
Kaposi's sarcoma had at least a slight response to the drug. The new trial
will make the drug available to 100 New York City patients with other
illnesses as well.
====================================================================
April 1, 1993
====================================================================
"HIV Vaccination Dilemma" Nature (03/18/93) Vol. 362, No. 6417, P. 212
(Sabin, Albert B.)
There is no scientific evidence that any of the experimental vaccines
against SIV or HIV, some of which are scheduled for use in large-scale human
trials, have any protective effect against natural modes of transmission in
previously uninfected or latently infected hosts, writes renowned polio
researcher Dr. Albert B. Sabin. In their commentary in Nature, Ada et al.
discussed a paper by Sabin on the improbability of effective vaccination
against HIV because of its intracellular transmission and rectal (or {*filter*}l
cervical) port of entry. Neither antibodies nor cell-mediated immunity (CMI)
is effective against intracellular transmission of HIV infection. Ada et al.
said that "cells in the donated {*filter*} already expressing viral antigen could
fuse with host cells (gp120/CD4 interaction), and thus be recognized by both
classes I MHC restricted CTLs resulting from the vaccination and alloreactive
CTLs." But the flaw in this argument is that there is a "novel way" by which
HIV-infected lymphocytes have been demonstrated to be capable of rapidly
transferring infectious virus, either HIV RNA or chromosomally integrated HIV
cDNA, in HIV-positive cells by cell-to-cell contact without using CD4
receptors. Ada and colleagues also said that "to delay or not to perform
such trials for the reason proposed by Dr. Sabin would be disastrous for the
increasing numbers of people exposed to the risk of infection." Sabin
concludes that what is dangerous is continuing the current inadequate methods
of study of HIV and SIV vaccines, and to carry out large-scale tests in humans
Health InfoCom Network News Page 49
Volume 6, Number 8 April 4, 1993
of vaccines without sufficient evidence that such vaccines can protect
natural infection with adequate doses of intracellular virus.
====================================================================
"Testing Times" Economist (03/20/93-03/26/93) Vol. 326, No. 7803, P. 90
Clinical-trial researchers have developed three methods to improve
clinical testing procedures. Currently, trials use small homogeneous groups
of test subjects under strict controls. Small trials of {*filter*} that only offer
mild improvements over existing {*filter*} often lead to inconclusive results, and
many small trials are necessary to notice the differences. People with fatal
diseases, such as AIDS, find that beneficial {*filter*} may not be available
because trials turn up inconclusive results, creating delays in drug
approvals. However, AIDS researchers have found that they can reduce the
length of clinical trials by using surrogate markers, which are measurements
showing the progression of the disease. The use of surrogate markers allows
researchers to determine the effectiveness of a drug without waiting for the
disease to run its course, as was the case with ddi and ddc that used levels
of CD4 as a marker. Another test procedure uses small trials to test for
toxicity. Researchers then administer the safe {*filter*} to patients while
doctors and drug firms monitor the patients' progress to determine the
effectiveness of the {*filter*}. A third testing method, known as randomised
heterogeneous mega-trials, uses a large number of subjects with different
backgrounds in bias-free trials.
====================================================================
April 2, 1993
====================================================================
"New Study Questions Use of AZT in Early Treatment of AIDS Virus" New York
Times (04/02/93), P. A1 (Altman, Lawrence K.)
Early treatment with the AIDS drug AZT for HIV infection may not be
necessary, according to a large European study published in this Saturday's
issue of The Lancet. The drug is prescribed to people infected with HIV long
before they develop full-blown AIDS. However, the new study did not find an
evident benefit in taking AZT early in the course of infection. The
research, which was conducted in England, France, and Ireland between October
1988 and October 1991, is known as the Concorde study. It was carried out at
65 medical centers in the three countries, and involved a total of 1,749 HIV-
positive people. Half of the volunteers were given AZT, while the other half
were given a placebo. The survival rate was 92 percent among those who were
treated immediately after diagnosis, and 93 percent among those who were
given a placebo. The study found the rate of progression from infection to
AIDS or death to be 18 percent in both groups involved. Dr. Dan Hoth, an
AIDS expert at the National Institute of Allergy and Infectious Diseases in
Bethesda, Md., said American scientists were expecting to meet soon with the
Health InfoCom Network News Page 50
Volume 6, Number 8 April 4, 1993
researchers who conducted the study to examine all the data. The meeting is
scheduled to be held in June in Washington, but until then, he said, "we see
no basis for making a change in the use of AZT in the current clinical
practice in the United States." Nick Partridge, head of the Terrence Higgins
Trust, an AIDS charity and advocacy group in Britain, said the new findings
could deter some people from getting tested for HIV if they believe there is
not an effective early treatment. Related Stories: Washington Post (04/02) P.
A1; Philadelphia Inquirer (04/02) P. A3; Financial Times (04/02) P. 1
====================================================================
"HIV Ambush: Studies Show the AIDS Virus Hides Out in Lymph Nodes Before it
Attacks" Time (04/05/93) Vol. 114, No. 14, P. 19
The belief that HIV lies dormant in HIV-positive individuals for the
greater part of infection has been disproved in two studies published in
Nature. The studies found that once infection has been established, the
virus immediately replicates millions of times in the lymph nodes--pea-size
organs located throughout the body. After main parts of the immune system
are eradicated, the excess amounts of the virus in the lymph nodes move into
the {*filter*}. Due to the massive hidden attack, it may make it impossible to
eliminate the virus from the body. The researchers suggest that these
findings emphasize the importance of preventing HIV infection as a means to
fight the spread of the deadly virus.
Health InfoCom Network News Page 51
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HICN608 Medical News Part 4/4