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Application of Ultraviolet Blood
Irradiation for Treatment of HIV and Other Bloodborne Viruses
by Carl Schleicher
Foundation for Blood Irradiation
Content:
Abstract
This paper describes an innovative method of inactivating blood-borne
viruses using ultraviolet blood irradiation called UBI therapy. This
process has shown impressive clinical results in treating hepatitis,
HIV, and other currently untreatable viruses. The background, theory,
and method of using UBI therapy is presented in this paper. This method
offers a potential break-through in the treatment of viral diseases and
bacteria, and is nontoxic, uses no drugs, and even has FDA
certification, and thus is available now for use.
Ultraviolet
blood irradiation first evolved in the early 1930s as a means to treat
persons afflicted with the poliovirus which was causing considerable
anguish and fear similar to the advent of the HIV in the 1980s and
continuing. Then in the 1950s the Salk vaccine wiped out polio in the
U.S. and, as a result of this fact and other reasons, this process fell
in disuse until recent years. This process has now been resurrected by
the Foundation for Blood Irradiation (FFBI) which had been originally
founded in the 1940s by the developers of this process, most of whom are
now deceased, who left this to the next generation of researchers to
continue.
Much credit for the early development of this technology goes to E.K.
Knott of Seattle, Washington; Louis Ripley of Danbury, Connecticut; and
Dr. T. Lewis of Pittsburgh, Pennsylvania.
Ultraviolet blood irradiation therapy (UBIT), or intravenous
ultraviolet, raises the resistance of the host and is therefore able to
control many disease processes. A fundamental effect of ultraviolet
blood irradiation is to "energize" the biochemical and
physiological defenses of the body by the introduction of ultraviolet
energy into the bloodstream that may, in part, be effective by producing
small amounts of ozone from the oxygen circulating in the blood.
The efficacy of this method is attested to by the remarkable and
consistent recovery of patients with a wide variety of diseases,
apparently unrelated etiologically. In addition, it may be stated that
UBI has never caused any adverse side effects nor has it ever worsened
any disease in any patient, regardless of age group, race or sex and
regardless of the number of blood irradiation treatments administered.
Furthermore, there have not been any complications related to UBIT
during long-term follow-up.
An average of 3.28 treatments per patient were administered in this
series. Laboratory studies were employed to confirm clinical
improvement, which occurred on an average of 19.2 days after institution
of blood irradiation therapy. Sixty percent of the patients were
considered clinically recovered and able to return to their occupation
in two weeks or less.
The older UBIT units have been updated and are now available and FDA
certified for use in the U.S. These units are being further evaluated
for improvements; this is being carried out under a CRADA (Cooperative
Research and Development Agreement) with the Lawrence Livermore National
Laboratories of Berkeley, California.
Steps are now being taken to arrange research protocols at several major
university medical research centers on both the East and West coasts of
the U.S. Focus will be on treatment of HIV, hepatitis, malaria, and
those viruses immune to current antibiotics.
Researchers in Russia have used this process to treat HIV with
impressive results. A copy of this report will be sent to those who
request it for the cost of photocopying. This report provides specific
details, clinical results, and improvements noted in the HIV-infected
patients in terms of CD4 T cells, leucocytes, etc. With respect to
treating HIV-positive persons, our clinicians also administer the
following natural products: ESSIAC, VENUREX (formerly Carnivora), and a
Czechoslovak produced product called Imuregen. Each of these are being
evaluated at NCI and NIAID per agreements we hold there.
Ultraviolet blood irradiation therapy (UBIT) is currently FDA approved
(and the treatment of choice) for cutaneous T-cell lymphoma (CTCL)
(Taylor & Gasparro, 1992). Using a technique based on extensive
historical experience with PUVA therapy in dermatology, Edelson and his
group at Yale have developed a sophisticated UBIT method involving
pretreatment with psolaren, extracorporeal leukopheresis, UV-A
irradiation of the white blood cell fraction, and reinfusion (Edelson,
1987). This process has been given the name "photopheresis."
Photopheresis is currently undergoing clinical trials at centers around
the country for the treatment of systemic sclerosis, multiple sclerosis,
rheumatoid arthritis, autoimmune insulin-dependent diabetes, systemic
lupus erythematosis, myasthenia gravis, graft versus host disease,
pemphigus vulgaris, and HIV associated disease (Edelson, 1991; Bisaccia
et al. 1990). The major drawbacks to photopheresis are that the
technique is cumbersome and costly; a single treatment occupies patient
and skilled technician for upwards of five hours.
Historically, the Knott technique of UBIT (Knott, 1948) was applied
extensively and with excellent results during the 1930s, 40s, and 50s
for the treatment of a wide variety of conditions. There are published
reports on its use in bacterial diseases, including septicemias,
pneumonias, peritonitis, wound infections; viral infections including
acute and chronic hepatitis, atypical pneumonias, poliomyelitis,
encephalitis, mumps, measles, mononucleosis, and herpes; circulatory
conditions including thrombophlebitis, peripheral vascular arterial
disease, and diabetic ulcer; overwhelming toxemias, non-healing wounds
and delayed union of fractures, rheumatoid arthritis, and a number of
others (Barger & Knott, 1950).
Schwartz and his colleagues in Chicago concluded a critical examination
of the Knott technique (Schwartz et al. 1952) by saying "a longer
and more extensive program of study is warranted before in vivo blood
irradiation of blood can be finally either accepted or rejected."
However, before such further examination could be undertaken, several
other factors intervened. Principal among these was the development of
antibiotics whose early successes made it appear that soon all
infectious diseases would be conquered by chemistry. In addition,
however, after World War II, there had been great interest in the
possibilities of employing UV light to sterilize blood and blood
products for transfusion (Oliphant & Hollaender, 1946; Wolf et al.
1947; Blanchard et al. 1948). When this effort failed after premature
approval in 1949 and subsequent commercialization, the whole field of
ultraviolet blood irradiation was quickly forgotten (Murray et al.
1955).
UBIT virtually disappeared from the early 1980s when the Soviets began
referring to the published work of Knott and his colleagues. In the
current listings of world medical literature at the National Library of
Medicine on UBIT (excluding photopheresis) there are over 100 articles,
and all of these are in the Soviet literature. Like Knott, it appears
that the Soviets have applied UBIT to a wide variety of conditions, but
only over the past two decades (Arutiunov, 1988).
We propose to reexamine the Knott technique with the advantage of vastly
improved technical and medical tools. Viral illnesses, given their
comparative resistance to chemotherapeutic control, have emerged over
the past several decades as a major challenge for medicine. In addition,
immune system dysfunctions are increasingly recognized as playing a
major "host factor" role in many disease processes, including
cancer. Given the range of potential applications of UBIT, a program of
study is warranted.
Rationale
There are many effects of ultraviolet light on blood components that may
be involved in clinical effectiveness. The interaction of various wave
lengths of ultraviolet with living tissues is complex and constitutes an
entire area of specialization for photobiologists (Coohill, 1991).
Applications of ultraviolet light are numerous in medical dermatology
(Morison, 1991). In particular, regimens employing UV-A (known as PUVA
when combined with the photosensitizing agents known as psoralens) and
UV-B (Anderson, 1984; Van Weelden et al. 1990) have been widely used in
the treatment of psoriasis and related skin eruptions. It was on the
basis of this long experience with PUVA therapy in humans that Edelson
developed photopheresis (Edelson, 1987).
In hematology, immunology, and blood banking, there is a long tradition
of exploring the possibilities of ultraviolet to produce beneficial
changes in blood components. UV has long been known to inactivate
viruses while preserving their ability to be used as antigens in the
preparation of vaccines (Levinson, 1945). The mechanism proposed being
that the viral genome is more UV-damage sensitive than viral surface
antigens. Thus, the virus can be killed by damage to its nucleic acids
while, at the same time, leaving antigenic surface components (proteins,
glycoproteins, and/or fatty acids) relatively intact.
In recent times, UV has been found to be a useful tool in the preventive
treatment of platelet-concentrate infusion-induced alloimmunization
reactions (Sherman et al. 1991; Pamphilon & Blundell, 1992), and for
the prevention of graft-versus-host reactions in transplantation (Leitman,
1989; Kapoor et al. 1992). Here the principal mechanism is thought to be
the sensitivity of lymphocytes (that typically contaminate platelet
concentrates and carry the HLA antigens responsible for the reactions)
to UV inactivation compared to the relative insensitivity of the
platelets (which lack nuclear material).
Since the advent of the AIDS epidemic, the blood banking industry has
been undergoing a revolution of increased sophistication. With the
vastly increased demand for guaranteed safety of blood products, many
methods of sterilization have been examined intensively (Horowitz, 1987;
Fratantoni & Prodouz, 1990). Among these, ultraviolet inactivation
of viruses contaminating blood and blood products has been studied (Fratantoni
& Prodouz, 1990). It is clear that with either PUVA or UV-B, most
viruses are quite UV-sensitive (Hanson, 1992). Current expert opinion,
however, is that viral inactivation sufficient for the purposes of the
blood banking industry (six or more logs of killing) is not feasible
without intolerable levels of damage to formed elements in the blood (Fratantoni,
1992; Dodd, 1992).
Meanwhile, there has been intensive examination of the mechanisms of
action of photopheresis by Dr. Edelson, his colleagues, and others (Edelson,
1989). The original inspiration for photopheresis was the work of Dr.
Cohen and his colleagues in Israel who demonstrated in animals that
selective damage to lymphocytes could "immunize" animals to
the development of autoimmune encephalomyelitis (Ben-Nun et al. 1981;
Holoshitz et al. 1983). The use of psoralen with UV-A to treat blood
outside the body was developed by Dr. Edelson as an improved method of
delivering just such selective damage to human lymphocytes. Thus,
lymphocyte damage remains the core mechanism invoked to explain the
clinical effectiveness of photopheresis. Following reinfusion, the
damaged cells appear to provoke a response from the immune system that
is therapeutic ­p; the exact details of which probably depending
on the nature of the conditions being treated.
Numerous other effects of "extracorporeal PUVA" have been
observed. Among these are mutations, inhibition of DNA synthesis,
changes in gene expression of various sorts, increased intracellular
Ca+2, the elaboration of cytokines IL1, IL6, and TNF, effects on
prostaglandins, and a variety of cell surface changes (Taylor &
Gasparro, 1992; Andreu et al. 1992).
Reviewing the early work by Knott and his colleagues, one of the most
striking findings was the rapidity with which cyanosis was cleared in
hypoxic patients following reinfusion of irradiated blood (Knott, 1948).
Miley and his colleagues at Hahnemann, looked at oxygenation in subjects
following reinfusion and showed significant increases in average values
at 10 and 30 minutes (and even 30 or more days) after reinfusion (Miley,
1939). There are no reports of measurements of oxygen potential of the
blood prior to reinfusion pre and post irradiation, however, and we are
left to presume that the dramatic observed increases in oxygenation were
due to some unexplained effect of the irradiated blood following
reinfusion.
There was speculation at the time that this might be associated with the
vasodilation that was observed clinically in approximately 75% of
treated cases and which appeared to persist for days and sometimes
months. Attempts to identify mechanisms for this effect would appear to
be a fruitful avenue of research for Phase II. To that end, in Phase I,
we will include in our TNF studies, blood gas determinations by
contemporary methods pre and post irradiation.
Before the first attempted human trial in 1928, Knott had determined
that red blood cells are very UV-hardy. A decade later, however, when
Knott studied the increased opsonic index of irradiated
polymorphonuclear cells (PNCs), he found that there was a narrow
therapeutic window for this effect ­p; "The time of exposure
from the point of peak PNC stimulation to the point of overexposure and
PNC destruction is a matter of only a few seconds." (Barger, 1944)
On the basis of these findings, Knott defined the strict treatment
parameters that he insisted upon subsequently in an attempt to stay
within the therapeutic window he had found. Replication of these
findings with UV dosimetric determinations would be another fruitful
avenue of research for Phase II.
Knott
Hemoirradiator Process
The Knott Hemoirradiator consists of a metal cabinet on rollers that
houses the power supply and pump mechanism for the water-cooled Burdick
UV lamp mounted on top of the machine. Blood is first collected by
conventional venipuncture into a citrated bottle. It is then routed
through a peristaltic pump mounted on the top of the instrument, through
the irradiation chamber, and back to the patient. There is a simple
panel on the front housing controls for the lamp voltage and the pump
speed. This is illustrated in Figure I.
The
Knott UBI Method
There are a number of features of the Knott instrument that distinguish
it from the photopheresis equipment currently being used clinically for
UBIT. Perhaps the most important difference is that the UV source in the
Knott device is a high-intensity quartz-mercury lamp with considerable
UV-B output (reported) as opposed to a relatively low-intensity
fluorescent UV-A, visible, and some IR remain comparatively poorly
studied. A special feature of the Knott instrument is that the blood
flow-rates reported for its use clinically were approximately 0.5
ml/sec. This means that treatment sessions with the Knott device of
around 250 ml of blood were completed in under an hour compared with the
up to 5 hours needed for modern photopheresis. Exposure times of the
blood to the UV were thus substantially less than with photopheresis.
Actual UV doses delivered remain to be determined.
A third distinguishing feature of the Knott device is that it was used
clinically with whole blood. There was no processing of the blood prior
to UV exposure to separate out various blood components for irradiation.
The rationale for removing the bulk of the red blood cells prior to
irradiation in photopheresis is to reduce the UV-shielding effects of
the strongly UV-absorbing hemoglobin pigments. What effects will be
observed with irradiation of whole blood remain to be studied.
A fourth feature is the irradiation chamber. This is a 5 cm diameter, 1
cm deep chamber with a number of baffles in it so as to create
turbulence in the blood flowing through it and expose it on one side to
the UV light. By comparison, the currently employed, patented Therakos
photopheresis "cassette" is a flat plastic container
approximately 12 X 20 cm square in which the leukocyte enriched blood in
this turbulent state is largely unknown. We can speculate, however, that
given the ultraviolet opacity of whole blood, cells will be exposed to
potentially effective doses of UV for at most 10% of their time
transiting through the irradiation cell. The effects of this brief and
intermittent exposure are unclear.
The Foundation for Blood Irradiation is now conducting training sessions
on ultraviolet blood irradiation therapy and can make these devices
available to those who may have an interest in using them.
In summation, this process represents a low cost, nontoxic, pain free
way to treat a variety of viral and bacterial diseases. The key
advantage is the low cost in doing so which could result in considerable
savings to the health industry. Future plans are in the works to apply
this process to other currently untreatable conditions, including
Alzheimer's, sickle cell anemia, and E. coli bacteria. Those who may
have an interest in working with the Foundation for Blood Irradiation in
these areas are requested to contact us.
Clinical
Results of Ultraviolet Blood Irradiation in Treating HIV-Positive
Persons
These results were obtained by using the PCR Diagnostic test (Polymerase
Change Reaction) which accurately determines change in viral activity.
These tests were done in April-June 1995 at a private clinic using our
ultraviolet blood device provided by the Foundation for Blood
Irradiation of Silver Spring, Maryland.
Patient
Dates of Treatment PCR Viral Activity
J.K. 5/8/95 654
5/18/95 340
D.G. 4/6/95 8900
4/27/95 1395
Note:
Each treatment of UBI reduced PCR by 50%-75%. This is considered a very
significant reduction. Additional clinical results will be available.
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