kdavis@lll-crg.llnl.gov (Ken Davis) (10/25/89)
AIDS TREATMENT NEWS Issue # 89, October 20, 1989
CONTENTS: [items are separated by "*****" for this display]
Mobilizing for Earthquake Relief: The Contrast with AIDS
DDI Correction and Update: Phone Number for Physicians
San Francisco, San Diego: Oral Ganciclovir Study
Dextran Sulfate Not Absorbed, Study Finds
San Francisco: AIDS Issues On November Ballot
AmFAR Will Fund AIDS Projects in Developing Countries;
Deadline November 30
Hemophilia Groups May Boycott or Move U. S. Conference
DDC: The Low-Cost Antiviral
*****
MOBILIZING FOR EARTHQUAKE RELIEF: THE CONTRAST WITH AIDS
Editorial by John S. James
The October 17 earthquake killed 10 people in the city of
San Francisco; the AIDS epidemic has killed over 200 times as
many here. Yet in two days, national institutions mobilized as
they have never done in eight years of AIDS. For example:
* No one imagines that when an earthquake or hurricane
strikes one part of the United States, other parts would turn
their backs and say it isn't their problem. Yet with AIDS,
impacted cities like San Francisco and New York are left to cope
on their own, largely without Federal help.
* When a mile-long section of Interstate 880 collapsed in
Oakland during the earthquake, killing dozens of people, no one
dreamed of delaying rescue efforts until someone could make money
off them. Yet when a life-threatening virus has infected hun-
dreds of thousands or more in the U. S., and millions in the
world, practically nothing moves in AIDS research until corpora-
tions smell profits, or academics get grants. Not five years
ago, not last year, not today.
We do not object to people being paid for their work, or
making reasonable profits. We do object to the nearly universal
practice of delaying critical research a year, two years, or
more, for the sake of financial arrangements -- and to the lack
of leadership which allows this practice to continue.
For over three years, AIDS TREATMENT NEWS has pointed to
obvious, inexpensive, and critical steps needed to save lives.
Usually we knew that nothing would be done. Therefore we have
had to focus on what people could do for themselves, with or
without institutional support.
The city official who called the earthquake the worst disas-
ter to strike San Francisco since 1906 -- overlooking the epi-
demic which has killed 200 times as many -- inadvertently
illuminated the crucial but overlooked fact that AIDS has not
been treated as a disaster. Outside of the immediately affected
communities, there isn't even a pale shadow of the mobilization
that the far less deadly earthquake has called forth.
How can we address the fundamental lack of national will to
save lives? Clarifying and explaining what should be done can
help. Protest and political action can help. But ultimately the
AIDS community cannot create mobilization which is not there, so
we will have to wait for people to become ready. We can only
continue to do our work as best we can, for as long as necessary.
*****
DDI CORRECTION AND UPDATE: PHONE NUMBER FOR PHYSICIANS
The last issue of AIDS TREATMENT NEWS gave an erroneous
phone number for physicians to call to register themselves to
obtain DDI for their patients. The correct number for physicians
only is 800/662-7999.
Anyone can obtain information about clinical trials of DDI
and other AIDS drugs by calling 800/TRIALS-A.
Our last issue correctly stated the three different doses of
DDI that will be used in the Treatment IND and the Open Safety
(compassionate use) programs, but we did not explain how the
doses will depend on body weight. The starting dose of DDI is
375 mg twice a day if patient weight is greater than or equal to
75 kg, 250 mg if 50-74 kg, and 167 mg if 35-49 kg. These doses
do not apply to children, as no one under 12 can receive DDI
through these programs.
For more information, see "DDI Trials, Access Announced," in
our last issue.
*****
SAN FRANCISCO, SAN DIEGO: ORAL GANCICLOVIR STUDY
An oral form of the anti-CMV drug ganciclovir (DHPG) will be
tested in patients in a phase I clinical trial. The trial will
take place in San Francisco and San Diego, and is now recruiting
volunteers. Until now, ganciclovir has only been given
intravenously -- a serious drawback since use of the drug must be
continued indefinitely.
One arm of the study will recruit 12 people with stable CMV
retinitis, to see if they remain stable when switched from IV to
oral ganciclovir. However, this part of the study may be filled
by patients already at the institutions running the trial.
The other arm needs 36 volunteers who are HIV positive, are
not now taking AZT, and do not have any symptoms of CMV infec-
tion. They will be tested for CMV in the urine, which they must
have in order to enter the trial. Then they will be given one of
three different doses of oral ganciclovir for 28 days, to see if
the drug can eliminate or reduce the virus in the urine. (The 12
patients with stable retinitis will only be given the highest
dose, to minimize the danger that the retinitis might progress.
For those who have no sign of infection except CMV in the urine,
however, it is safe to test lower doses.)
Volunteers may have used AZT before, but not during the last
28 days; they should not go off AZT in order to enter this study.
The reason for excluding AZT is that it usually cannot be com-
bined with ganciclovir, because both can cause bone- marrow toxi-
city. Volunteers must not now have active PCP, cryptococcal men-
ingitis, severe diarrhea, or certain other conditions. They must
have over 1000 neutrophils and over 50,000 platelets, and must be
between 18 and 60 years old. There may also be other conditions.
The study will last 28 days. Volunteers will spend the
first two days in the hospital for tests, then come in for daily
visits for one week. There will be one whole day of hospitaliza-
tion after 2 weeks, and 24 hours at the end of the trial. There
is no cost to participate in this study.
In San Francisco, patients can volunteer at any of three
different medical centers depending on their preference. At San
Francisco General, call Chris Kimbrell, 821-5089. At Davies,
call Brian Christenson, 565-6153. At Mt. Zion, call Karen Tay-
lor, 885-7432.
In San Diego, the oral ganciclovir study is not yet open to
enroll volunteers. When it is ready, people will probably call
the University of California San Diego, Treatment Center,
619/298- 7021.
Historical Note
Oral ganciclovir has existed for years, but has not been
developed, apparently because of the confusion over the official
status of the intravenous form of the drug (see "CMV Retinitis --
Ganciclovir, Foscarnet, and Other Treatments: Background, His-
tory, and Emerging Controversy," AIDS TREATMENT NEWS #71,
December 16, 1988). Intravenous ganciclovir was officially
approved for marketing as a treatment for CMV retinitis on June
26. Before then, it had been given free to thousands of patients
under compassionate use.
A study published over two years ago showed that the drug
could be given orally and produce a high enough blood level to
inhibit CMV (Jacobson, M. A. and others, "Human Pharmacokinetics
and Tolerance of Oral Ganciclovir," Antimicrobial Agents and
Chemotherapy, August 1987, pages 1251-1254). However, only about
three percent of the drug is absorbed, and it is not clear that
oral use will be feasible; that is the question the current study
seeks to answer.
At least two other oral drugs to treat CMV -- FIAC, and
HPMPC- -are being developed. (For background on HPMPC, see AIDS
Treatment News #76, March 24, 1989.)
Oral ganciclovir could have been developed any time during
at least the last two years, and probably much longer. Approval
of the intravenous drug, plus the development of potential com-
petitors, provided a motive for it to be developed now. As in
almost all such cases, no one represented the patients' interest
in the matter, as both AIDS organizations and practicing physi-
cians chose not to involve themselves in treatment research and
development issues.
*****
DEXTRAN SULFATE NOT ABSORBED, STUDY FINDS
A small trial at Johns Hopkins University found that less
than one percent of dextran sulfate taken orally by healthy
volunteers was absorbed into the bloodstream -- suggesting that
taking the drug orally is unlikely to be useful. This informa-
tion, published October 1 in the Annals of Internal Medicine, is
not new, but was announced in February by Frank Young, M. D.,
Commissioner of the Food and Drug Administration. It took until
now to be formally published.
The research team used three different tests to measure the
level of dextran sulfate in the blood. Only one of the methods
detected any of the substance after oral use, and the amount was
small. By contrast, all three methods showed large amounts of
dextran sulfate after intravenous administration.
The researchers suggested that future studies administer the
drug that way. They themselves are doing so in a small study
(see AIDS TREATMENT NEWS #86, August 25, 1989). Incidentally,
this study still needs volunteers; persons interested can call
Linda Nerhood at 301/955-7703, or Charles Flexner, M. D., at
301/955-9712.
After the early an|]wncement by the FDA that oral dextran
sulfate was probably not absorbed, sales fell greatly. One
buyers' club reported a drop in total sales of 80 percent. Some
people have continued to use dextran sulfate, however, and some
of them are convinced that it is helping.
Comment
To us, the history of dextran sulfate shows that the AIDS
community can respond appropriately and very rapidly to new
information when it is made available in a useful way -- in this
case, by an authoritative announcement from the FDA. Persons who
were interested in the drug learned immediately that serious
doubt had been raised about its value.
But some people have chosen to continue using dextran sul-
fate, even though they know about the absorption results, because
they believe that the drug is helping them. This action seems
sensible, too. Much is still unknown; for example, it is con-
ceivable that the drug might help some people even if it does not
get into the bloodstream, by coming into direct contact with HIV
infection in the gastrointestinal tract. Theories are only
guides, which may be more or less helpful; ultimately what is
important is what works.
Unfortunately a very different conclusion was drawn by one
of the researchers who did the absorption study. Paul S. Liet-
man, M. D., Ph.D., criticized the FDA for allowing patients to
obtain unapproved drugs for persons use -- both in an Associated
Press story October 2, and in a Johns Hopkins University press
release issued a few days later. He called such access "a step
backward," saying that "it is wrong to provide drugs of unproven
value to patients with devastating diseases."
The AIDS community first learned about dextran sulfate over
two years ago, when laboratory results suggested that it was one
of the best anti-HIV substances yet found. Patients knew that
millions of people had used it orally in Japan, where it had been
found safe enough to have been sold for 20 years without a
prescription. There were doubts about absorption, but it seemed
unlikely that millions of Japanese had fooled themselves for 20
years and taken a useless drug. Patients also knew that if the
drug did work, it would probably take years to be approved in the
United States (in fact it did take two years just for a test for
absorption, and for an intravenous trial to start). And with the
drug's extensive safety record, the AIDS treatment community knew
that the consequences of using it and being wrong would probably
be small -- whereas not using it and being wrong could easily
have cost tens of thousands of lives.
Based on what was known at the time, the decision to obtain
dextran sulfate from Japan and use it seems clearly to be the
rational one. Conversely, the decision to wait for approval
might have been suicidal.
We now know that dextran sulfate when taken by mouth is not
promising. But decisions must be made on what was known at the
time, not what is known two years later. By this standard, we
think that the AIDS community has handled dextran sulfate well --
and that calling for police power to prevent people from making
rational and compelling decisions about their health care is not
helpful.
*****
SAN FRANCISCO: AIDS ISSUES ON NOVEMBER BALLOT
by John S. James
At least two ballot initiatives in San Francisco are
relevant to AIDS. It is urgent to get out the vote, because
off-year elections are generally weighted toward conservative
voters who are least sympathetic toward AIDS.
Community-Based Research and Service -- Proposition U
This initiative, organized by Mobilization Against AIDS,
declares that it is the policy of San Francisco to support com-
munity organizations conducting medical research and AIDS ser-
vices. There is no legally binding effect. Supporters signing
the official ballot argument include the executive directors or
comparable officials of Mobilization Against AIDS, San Francisco
AIDS Foundation, AIDS Activities at San Francisco General Hospi-
tal, Black Coalition on AIDS, American Indian AIDS Institute,
Latino Coalition on AIDS/SIDA, and Project Inform. There is no
organized opposition.
Paul Boneberg of Mobilization Against AIDS said that the
reason for the initiative was to put a pro-active measure on the
ballot -- to give the public a chance to vote for a positive AIDS
measure. If it gains solid support, more substantive initiatives
can be developed in the future.
While passage is probably assured, the size of the vote will
be important. And Proposition U is hampered by lack of public
familiarity with community-based research, lack of publicity
about the ballot measure, and the fact that many AIDS organiza-
tions refused to sign the voter handbook arguments for fear of
being "political."
Domestic Partners -- Proposition S
This measure is not supposed to concern AIDS, but in fact it
does.
A domestic partners ordinance, passed unanimously by the San
Francisco Board of Supervisors and signed by the Mayor, would
already be law except for a campaign by conservative religious
leaders, who obtained signatures of over ten percent of the
voters, requiring the law to be submitted to voters in an elec-
tion. The measure would allow unmarried couples to formally
register their relationship; they would agree to be jointly
responsible for their living expenses, and they would be given
the same hospital visitation rights (and bereavement leave, for
City employees) as married couples.
While supposedly unrelated to AIDS, this measure has in
effect become a referendum on the gay community, as a reading of
the ballot arguments opposed to it will show. (In one of the
official arguments, the word "unnatural" is used three times in
two short paragraphs -- and "morally reprehensible" once -- to
apply to gay relationships.) Since San Francisco's model AIDS
program would not exist without the strength of the gay community
here, we are concerned loss of this vote would undermine the
City's commitment to AIDS services.
Polls show that most San Francisco voters support domestic
partners, but a majority of the conservative voters who vote in
off-year elections do not. Therefore, getting out the vote is
the key to success of this measure.
Voters who cannot get to the polls can vote by mail, but the
application must be received by the Registrar of Voters no later
than October 31. For more information, call the Registrar of
Voters, 554-4375, or call the Yes on S campaign, 864-0860.
Volunteers are urgently needed, especially starting Friday,
November 3. For information call Yes on S, at the number above.
Note: Yes on S suspended campaigning for one week to sup-
port the Red Cross in earthquake relief. The campaign mobilized
over 110 volunteers and raised over $20,000 for the earthquake
effort.
*****
AMFAR WILL FUND AIDS PROJECTS IN DEVELOPING COUNTRIES;
DEADLINE NOVEMBER 30
The American Foundation for AIDS Research (AmFAR) announced
a new program to fund AIDS projects carried out in the developing
world by non-governmental organizations. Areas of interest
include educational projects for professional or lay audiences
carried out by local service providers, and small-scale projects
to facilitate communications and information exchanges on AIDS.
The deadline for letters of interest (not longer than two
pages) is November 30, 1989. Letters may be sent by fax to (U.
S.) 212/719-0712.
For a copy of the September 26 announcement of this program,
or for other information, contact Mervyn F. Silverman, M. D., M.
P. H., Chairman, International Committee, at the above fax
number. Or phone AmFAR at 212/719-0033.
*****
HEMOPHILIA GROUPS MAY BOYCOTT OR MOVE
U. S. CONFERENCE
by John S. James
On September 15, the UK Hemophilia Society wrote all member
organizations of the World Federation of Hemophilia that it could
not participate in the biannual hemophilia conference planned for
August 1990 in Washington, DC, because of the exclusion of per-
sons who are HIV positive from entry to the United States. Most
persons with hemophilia are HIV positive, because they were
infected by blood products years in the past before blood was
screened for HIV.
In May of 1989 the U. S. Immigration and Naturalization Ser-
vice (INS) instituted a 30-day waiver to allow HIV-positive per-
sons to visit the United States for purposes including attending
conferences, obtaining medical treatment, and visiting family
members (not for tourism). The UK Hemophilia Society is con-
cerned that to obtain this waiver, persons must declare their HIV
status and can then be singled out for discrimination. And "peo-
ple with hemophilia are immediately identifiable as potential
targets" because they are carrying supplies of blood products.
The letter urged that the conference be moved out of the U. S.
unless the law was changed.
It is generally believed that there is no chance that
Congress will repeal the provision in the foreseeable future.
For HIV-positive persons visiting the United States, the
National Gay Rights Advocates in San Francisco has published a
62-page guide on how to obtain the waiver. The INS wants appli-
cations 30 to 60 days in advance, but may accept an application
after an attempt to enter the United States if the applicant can
establish that he or she did not know about the need to apply.
There is no routine testing at the border, but the INS can
require testing for entry if it has reason to suspect that a per-
son is HIV positive -- for example, if AZT or medical records
suggesting HIV are found in a search of the luggage.
Obtaining the waiver is burdensome. Applicants must show
that they are not a danger to public health and can pay for any
medical care they may need in the United States, so that there
will be no cost to any government here. Extensive documentation
is suggested for supporting the application, and anything not in
English must be translated and properly certified by the transla-
tor. The National Gay Rights Advocates urges anyone to obtain
legal advice before submitting an application, because applying
can affect all future entry into the United States, whether the
waiver is granted or not.
For more information, see Visiting the USA: A Legal Guide
for Persons with HIV, available for $10. from the National Gay
Rights Advocates, 540 Castro St., San Francisco, CA 94110, or
call 415/863-3624.
History
The law excluding persons with HIV was passed in 1987. It
was introduced by Senator Jesse Helms (Republican, South Caro-
lina) as an amendment to the bill to pay temporarily for AZT for
persons with AIDS who had no other way to afford it. The exclu-
sion law was passed almost unanimously by Congress, in part as a
political trade to obtain the funds for AZT.
In April 1989, Dutch AIDS educator Hans Verhoef was jailed
for several days in St. Paul, Minnesota when he tried to enter
the United States to attend a medical conference in San Fran-
cisco. The local INS granted a waiver, but the Washington DC
office overruled the local and denied it. An immigration judge
then overruled the national office and granted the waiver, and
Mr. Verhoef arrived at the conference as it was ending.
Before the Verhoef case, the law had not attracted attention
in the United States. But in a bizarre incident several months
earlier, at least one Canadian had been turned back when trying
to enter the United States to obtain medical treatment. This
case was front-page, mainstream television news in Canada, but
completely blacked out in the United States; as far we can deter-
mine, no U. S. news organization reported the story, despite the
fact that it very much concerned this country.
The Verhoef case led to widespread concern that the interna-
tional AIDS conference scheduled for June 1990 in San Francisco
would be disrupted by detention of persons trying to attend.
Conference organizers pressured Washington for some way to keep
that from happening. The result was a May 25, 1989 INS memo
intended to codify a waiver policy. This is where the matter has
stayed since.
Very few people have yet applied for the waiver, so there is
little precedent to indicate what documentation the INS will and
will not accept as sufficient, or how much the decision will
depend on individual officials.
Comment
Foreigners are justifiably outraged by the U. S. exclusion
policy because the U. S. is a net exporter of HIV -- and also is
violating World Health Organization principles which the United
States itself agreed to.
Perhaps the greatest harm from the exclusion of HIV-positive
visitors is that it creates an incentive all over the world for
people not to step forward for testing within their own countries
if they suspect that they might be HIV-positive. Because of the
potential economic, personal, and medical importance of being
able to enter the United States, and the difficulty and uncer-
tainty of the waiver process, many people will find a clear
advantage in not knowing their status and ignoring the issue as
long as possible. Therefore many people will not know to obtain
early treatment if they need it, and not interact with public-
health authorities on how to avoid further transmission.
The June 1988 report of the Presidential Commission on the
Human Immunodeficiency Virus Epidemic -- the famous "Watkins Com-
mission" report, probably the most authoritative recommendation
on U. S. AIDS ever written -- made nondiscrimination protection a
cornerstone of efforts to control the epidemic, so that citizens
would come forward and cooperate with public health programs.
But now the United States itself is threatening citizens of all
other countries with potentially serious consequences for doing
just that. Its discriminatory policy creates a hidden disruption
in the public health program of every country on Earth whose
citizens are free to visit the United States.
*****
DDC: THE LOW-COST ANTIVIRAL
DDC is an antiviral closely related to DDI, which is widely
considered to be one of the most promising new AIDS treatment.
DDC may be as effective as DDI, and is currently undergoing
large-scale clinical trials sponsored by Hoffmann-La Roche (see
two articles in AIDS TREATMENT NEWS #81, June 16, 1989). And DDC
costs hundreds of times less than DDI to manufacture, meaning
that its potential cost, pennies a day, is within reach of every
person in the United States, and of every government in the
world.
About two years ago, DDC was found to cause serious peri-
pheral neuropathy in some patients, and therefore many people
gave up on the drug. But now it appears that DDC may be effec-
tive in doses much lower than were previously used, and that at
these low doses, the toxicity may be rare, and easily manageable
when it does occur. We may not have an ultimate answer until the
current large-scale trials are completed; these trials are
expected to take two years (see "Why No Antivirals: A Case His-
tory of Failed Trial Design," in AIDS TREATMENT NEWS #81, cited
above). But at least 300 people have so far taken DDC in clini-
cal studies -- and others have used "underground" DDC -- and
there appears to be enough information available now to make
practical decisions. Since most of the world's people with HIV
have no access to treatment because of economic obstacles, a drug
which eliminates these obstacles deserves careful attention.
The true cost of a drug must include not only the cost of
manufacture, but also any other costs of appropriate use, includ-
ing detection and management of side effects. For example, the
cost of using AZT must include the cost of blood tests for hema-
tological toxicity, of transfusions when needed, and of the
Western medical infrastructure which makes this technology avail-
able. But with DDC, the management of toxicity consists largely
in not exceeding the proper dose, and stopping the drug immedi-
ately if neuropathy does develop (treatment may be resumed later
at lower doses). The management of toxicity, therefore, has lit-
tle or no economic cost. And this drug does not require the
expensive infrastructure of Western medicine; instead, it might
be delivered through the traditional healers which are already in
place in most cultures.
In the United States, the government has claimed exclusive
worldwide rights to DDC as an AIDS treatment, and licensed these
rights to Hoffmann-La Roche. We checked with a patent attorney,
and learned that patent rights are in fact highly geographical,
and that it would probably be entirely legal to manufacture DDC
for medical use in many countries. In addition, DDC can only be
covered by a "use patent" (the weakest of all patents), since the
chemical has been commercially available and has been known for
over 20 years. A use patent for a drug is violated only at the
time of ingestion.
In the United States, DDC was available as an "underground"
drug over a year ago, but few people used it because of fear of
its toxicity. The most serious side effect is peripheral neuro-
pathy, often noticed first as pain in the feet. However, the new
clinical trial is using a very low dose, .01 milligram per kilo-
gram of body weight three times a day. This dose is less than a
quarter of what the U. S. "underground" has been using even
recently, which itself is much less than the doses which caused
serious side effects in the first clinical trials, before it was
known how little of the chemical was effective. This .01 dose --
which has enough preliminary evidence for efficacy that a major
corporation is willing to test it in hundreds of people -- is so
low that for persons of average weight, a single gram of DDC will
last for well over a year.
In the U. S., both DDC and DDI have sold for about the same
price, about $30,000 per kilogram. For DDI, this price
translates to hundreds of dollars a month. But DDC is used in
such small doses that it will usually cost under 10 cents a day.
(Note: the DDC which has been on peoples' shelves for the last
year or more may have deteriorated, and must be tested before
use.)
The official trials of DDC will probably take at least two
years to complete. Meanwhile, the AIDS community may want to
develop DDC as a treatment for those who have no other option.
The whole continent of Africa has been written off, ignored in
drug-development decisions because it cannot pay what U. S. com-
panies want to charge for their drugs. Within the U. S., minor-
ity groups are also likely to be written off -- and many people
from all social classes who cannot use AZT will fall through the
cracks of the DDI trials and parallel-access system.
DDC might be as good a treatment as any that exists today;
and it is readily available and there are no economic barriers to
its use. But it is also dangerous, and successful ways of using
it will not happen automatically; they must be systematically
developed. In different countries, for example, the drug would
need to be integrated differently into existing health systems.
We published this article to point out these possibilities.
We call on development experts, AIDS organizations, and others to
examine new systems for providing state-of-the-art treatment now,
without waiting for bureaucracies to move, for corporations to
find profit, or for the time required for national health care to
be established, or for a Western medical infrastructure to be
created where it does not now exist.
*****
STATEMENT OF PURPOSE
AIDS TREATMENT NEWS reports on experimental and complementary
treatments, especially those available now. It collects informa-
tion from medical journals, and from interviews with scientists,
physicians, and other health practitioners, and persons with AIDS
or ARC.
Long-term survivors have usually tried many different treatments,
and found combinations which work for them. AIDS TREATMENT NEWS
does not recommend particular therapies, but seeks to increase
the options available.
We also examine the ethical and public-policy issues around AIDS
treatment research and treatment access.
HOW TO SUBSCRIBE TO AIDS TREATMENT NEWS
Send $100.00 per year for 26 issues ($150.00 for businesses and
organizations), or $30.00 reduced rate for persons with AIDS or
ARC who cannot afford the regular rate, to: ATN Publications, P.
O. Box 411256, San Francisco, CA 94141. A six-month subscription
(13 issues) is $55.00 ($80.00 for businesses or organizations),
or $16.00 reduced rate. For subscription information and a sam-
ple issue, call 415/255-0588.
For the complete set of over 80 back issues, call AIDS TREATMENT
NEWS for information. The back issues include articles on DDI,
compound Q, fluconazole, AZT, aerosol pentamidine, ganciclovir
(DHPG), diclazuril, DHEA, lentinan, peptide T, passive immunoth-
erapy, and many other treatments.
To protect your privacy, we mail first class without mentioning
AIDS on the envelope, and we keep our subscriber list confiden-
tial.
Outside North America, add $20.00 per year for airmail postage,
and $18.00 airmail for back issues. Outside U. S. A., send U. S.
funds by International Postal Money Order, or by travelers
checks, or by drafts or checks on U. S. banks.
Copyright 1989 by John S. James. Permission granted for non-
commercial reproduction.
--
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