Descartes 466 Int. A, Col. Villa Universidad, C.P. 80010 Culiacán, Sinaloa, México
+52 (667) 753-1584


Culiacán, Sin. México, DF.

Application of Ultraviolet Blood Irradiation for Treatment of HIV and Other Bloodborne Viruses

Título
Application of Ultraviolet Blood Irradiation for Treatment of HIV and Other Bloodborne Viruses
Autores

Carl Schleicher

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 actor” 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.” (Barger1944) 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.
Regresar

Leave a reply