|Publication number||US20060155349 A1|
|Application number||US 11/354,788|
|Publication date||Jul 13, 2006|
|Filing date||Feb 15, 2006|
|Priority date||Aug 10, 2001|
|Also published as||DE60138656D1, EP1420857A1, EP1420857B1, US7226470, US20040030368, US20040204747, US20060111760, US20060136019, US20060235492, WO2003013653A1|
|Publication number||11354788, 354788, US 2006/0155349 A1, US 2006/155349 A1, US 20060155349 A1, US 20060155349A1, US 2006155349 A1, US 2006155349A1, US-A1-20060155349, US-A1-2006155349, US2006/0155349A1, US2006/155349A1, US20060155349 A1, US20060155349A1, US2006155349 A1, US2006155349A1|
|Inventors||Lajos Kemeny, Zsolt Bor, Gabor Szabo, Ferenc Ignacz, Bela Racz, Attila Dobozy|
|Original Assignee||Lajos Kemeny, Zsolt Bor, Gabor Szabo, Ferenc Ignacz, Bela Racz, Attila Dobozy|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (37), Referenced by (5), Classifications (17)|
|External Links: USPTO, USPTO Assignment, Espacenet|
This application is a continuation of U.S. application Ser. No. 10/410,690, filed Apr. 9, 2003, which is a continuation of International Application No. PCT/HU01/00102, filed Oct. 24, 2001, which claims priority from Hungarian Application No. P0103279, filed Aug. 10, 2001, all of which are incorporated herein by reference.
1. Field of the Invention
The present invention relates to the treatment and prevention of inflammatory and hyperproliferative diseases of body cavities, more particularly to the treatment and prevention of diseases of the nasal cavity by phototherapeutical methods.
2. Description of the Related Art
The treatment and prevention of inflammatory diseases of the nasal mucous membrane and paranasal sinuses is an unsolved problem. These diseases include allergic rhinitis, commonly referred to as hay fever, vasomotor rhinitis, non-allergic eosinophilic rhinitis, chronic sinusitis, which is the inflammation of the paranasal sinuses, and nasal polyps.
Rhinitis is an inflammatory disorder of the nasal mucous membrane, which is characterized by nasal itch, sneeze, nose running, nasal blockage, and rarely by loss of smelling. The inflammation of the nasal mucous membrane is frequently associated with the inflammation of the paranasal sinuses (rhinosinusitis, chronic sinusitis). As a consequence of the frequent and persistent inflammation of the mucous membrane hyperproliferative lesions, or so-called polyps develop on the mucous membrane.
One characteristic disease is the allergic rhinitis, commonly referred to as hay fever. The allergic rhinitis is the most frequent allergic disease affecting 10-20% of the population. The number of patients with allergic rhinitis, especially in the well developed industrial countries increased very rapidly in the last few years. Because of the high number of patients the direct and indirect costs of this disease are great.
Although hay fever is not a very severe disease, its unpleasant symptoms worsen the quality of life considerably. Hay fever is frequently associated with allergic conjunctivitis and sometimes with general symptoms. The symptoms last only for a few months in some patients (seasonal rhinitis), while in others they last the whole year (perennial rhinitis).
The symptoms of the allergic diseases develop as follows. An allergen enters the body and induces the production of a specific IgE, which binds to specific receptors on the surface of mast cells. After subsequent exposure the allergen crosslinks the IgE receptors, resulting in mediator release from the mast cells. These mediators are responsible for the development of the symptoms in patient.
As a result of this activation histamine and other preformed mediators are released from the mast cells. In the mast cells new inflammatory mediators are produced attracting further inflammatory cells into the mucous membrane (Howarth P H, Salagean M, Dokic D: Allergic rhinitis: not purely a histamine-related disease. Allergy 55: 7-16, 2000).
At present there is no known treatment for rhinitis. The increased number of inflammatory cells in the nasal mucous membrane release mediators, which are responsible for the clinical symptoms. Often antihistamines are used locally or systemically for the blocking of the released mediators. Sodium cromoglycate is available for the inhibition of the release of mediators. Finally, corticosteroids are used locally or systemically for the blocking of the synthesis of new mediators. In special cases a desensitizing therapy might be used. The pathogenesis of the development of the clinical symptoms is already well known. However, the presently available drugs often do not eliminate the symptoms. Therefore, every new method for the treatment of this disease has a great medical significance.
A further characteristic disease is vasomotor rhinitis. Vasomotor rhinitis is an inflammatory disorder of the nasal mucous membrane with unknown origin. The clinical symptoms are largely similar to that of allergic rhinitis: permanent nasal blockage, nasal itch, sneeze, nose running, and rarely loss of smelling. Mastocyte-activating mediators cause the symptoms. These are released from the nerve endings of the nasal mucous membrane upon irritation.
A further characteristic disease is the nonallergic eosinophilic rhinitis. This disease is characterized by the high number of eosinophils in the nasal secretions and by the lack of an allergic origin. The disease is frequently associated with the development of nasal polyps, the hyperproliferative condition of the nasal mucous membrane. The clinical symptoms are the same as in allergic rhinitis.
Additional diseases are rhinosinusitis and sinusitis. The inflammation of the paranasal sinuses is frequently associated with the inflammatory condition of the nasal mucous membrane (nasosinusitis). The isolated inflammation of the paranasal sinuses is also a frequent disease (sinusitis). This disease has often an allergic origin, although its exact cause remains unknown. There is no well-tested treatment, thus usually the same therapy is used as for rhinitis.
Ultraviolet light has been used for more than twenty years for the treatment of allergic and auto-immune skin diseases. In various treatments and procedures ultraviolet-B light (280 nm-320 nm) and ultraviolet-A light (320 mn-400 nm) is used typically. The ultraviolet light inhibits the antigen-induced cellular immune response and is able to induce tolerance (Streilein J W, Bergstresser P R: Genetic basis of ultraviolet-B on contact hypersensitivity. Immunogenetics 27: 252-258, 1988).
The ultraviolet light suppresses the immune reaction by inhibiting the antigen presentation and by inducing T-cell apoptosis. Irradiation of the skin with ultraviolet-B light or ultraviolet-A light on an area previously photosensitized by psoralen is known to inhibit the immunological processes in the skin. For the treatment of skin diseases there are a number of phototherapeutical devices available.
These phototherapeutical devices include ultraviolet light sources. These light sources might be classified based on, for example, their operational principle, output energy or power, mode of operation (impulse or continuous), and whether they are emitting monochromatic or multiwavelength light.
In early treatments broad band ultraviolet B (BB-UVB) light sources were used. In recent years more efficient narrow band ultraviolet B (NB-UVB) light sources became popular (Degitz K, Messer G, Plewig G, Rocken M: Schmalspektrum-UVB 311 nm versus Breitspektrum-UVB. Neue Entwicklungen in der Phototherapie. Hautarzt 49: 795-806, 1998).
Our previous investigations of psoriatic patients indicated that the 308 nm xenon chloride excimer laser is more effective for phototherapeutical treatments than the NB-UVB light sources (Bnis B, Kemny L, Dobozy A, Bor Zs, Szab G, Igncz F: 308 nm UVB excimer laser for psoriasis. Lancet 35: 1522, 1997; Kemny L, Bnis B, Dobozy A, Bor Z, Szabo G, Ignacz F: 308-nm excimer laser therapy for psoriasis. Arch Dermatol. 137: 95-96, 2001).
Phototherapeutical treatments improved significantly with the appearance of ultraviolet light delivering optical systems. Such an ultraviolet light delivering phototherapeutical system with fiber optic is used in the Saalmann Cup instrument, in which the concentrated ultraviolet light is coupled into a fiber optic cable. Therefore, it is suitable for the treatment of smaller lesions of the skin or mucous membrane (Taube K M, Fiedler H: Hochkonzentrierte UV Bestrahlung kleiner Hautbezirke mit einem neuen Punktstrahler. Grundlagen und klinische Ergebnisse. Deutsche Dermatologe, 10: 1453, 1992).
However, the Saalmann Cup can not be introduced into smaller body cavities because of its large contact area and because of the thickness of the used fiber optic cable. This device can be used in body cavities where the distal end of the fiber optic cable and the area to be treated can be visually controlled, such as the oral cavity. For this reason, this device is unsuitable for the treatment of body areas, which cannot be visually controlled, such as the nasal and paranasal mucous membrane, the gastrointestinal, and the urogenital mucous membrane.
Although ultraviolet light has been used for the treatment of hyperproliferative and inflammatory skin diseases for many years, it has not been used for the treatment of common, immunologically mediated disorders of the nasal mucous membrane. Neuman and Finkelstein used narrow-band, low energy, red-light phototherapy for the treatment of the nasal mucous membrane and they found it effective for perennial allergic rhinitis and for nasal polyposis (Neuman I, Finkelstein Y Narrow-band red light phototherapy in perennial allergic rhinitis and nasal polyposis. Ann Allergy Asthma Immunol 78: 399-406, 1997).
There are a number of ultraviolet light delivery systems, which use lasers. For example, the light of the 308 nm xenon chloride excimer laser can be guided by fiber optic cable for the cleaning of root canals by ablation (Folwaczny M, Mehl A, Haffner C, Hickel R: Substance removal on teeth with and without calculus using 308 nm XeCl excimer laser radiation. An in vitro investigation. J. Clin. Periodontol 26: 306-12, 1999). The 308 nm xenon chloride excimer laser is also suitable to treat artherosclerosis by treating the blood vessel walls (U.S. Pat. No. 4,686,979), or to enhance the cardiac oxygenization with transmyocardial laser revascularisation (U.S. Pat. No. 5,976,124), or inhibiting neovascularisation during angioplasty by destroying myocardial cells (U.S. Pat. No. 5,053,033).
These systems share the common feature that the high-energy ultraviolet light at the end of the light delivering system is focused on small areas of only a few hundred microns in diameter. This intense ultraviolet light carries out its effect by breaking some of the chemical bonds. However, the intense ultraviolet light damages the tissues with its ablative effect.
It is also known that larger skin lesions can be treated by using a number of small fiber optic cables (U.S. Pat. No. 6,071,302; WO9607451, Asawanonda P, Anderson R R, Chang Y, Taylor C R: 308-nm excimer laser for the treatment of psoriasis: a dose-response study. Arch Dermatol 136: 619-24, 2000).
Phototherapeutical systems attached to endoscopes are also used for the photodynamic treatment of tumors, such as bladder carcinoma or bronchial cancer. However, in these instruments no ultraviolet light is used, and they have special distal ends for tumor treatment (U.S. Pat. Nos. 4,313,431; 4,612,938; 4,676,231; 4,998,930; 5,146,917).
At present, the phototherapeutical systems delivering ultraviolet light consist of a hand piece specifically shaped to a special problem. As such, they are either unsuitable or inconvenient for the treatment of small body cavities such as the nasal cavity with visual control.
Finally, only the light of small concentrated ultraviolet light sources can be coupled with good efficiency into thin optical fiber cables, which have a diameter of a few tenth of millimeter. Ultraviolet lasers are suitable for this purpose, but they are expensive.
Briefly and generally, embodiments of a phototherapeutical apparatus are described, the apparatus including: an ultraviolet light source, operable to generate ultraviolet light, an optical guidance system, operable to receive and guide the ultraviolet light of the light source, and a patient interface, operable to receive the guided light from the optical guidance system, wherein the patient interface is insertable at least partially into a body cavity and is operable to apply the guided ultraviolet light to a tissue surface of a body cavity.
Further, embodiments of a method of treating diseases is described. The method includes providing a phototherapeutical apparatus, which contains an ultraviolet light source, an optical guidance system, coupled to the ultraviolet light source, and a patient interface, coupled to the optical guidance system. The method further includes preparing for the application of the phototherapeutical apparatus, inserting at least partially the patient interface into a body cavity, generating ultraviolet light with the ultraviolet light source, coupling the generated ultraviolet light into the patient interface through the optical guidance system, and applying the ultraviolet light by the patient interface to a tissue surface of a body cavity, wherein the tissue of the body cavity has an inflammatory disease or a hyperproliferative disease.
Examples of inflammatory diseases include the inflammatory diseases of the nasal cavity. Research showed that single or repeated irradiation of the nasal mucous membrane and paranasal sinuses with ultraviolet light with different wavelengths (UVB and UVA) inhibit the clinical symptoms of rhinitis, sinusitis and rhinosinusitis and result the regression of nasal polyps.
In some embodiments of the phototherapeutical method photochemotherapeutical methods are included, such as using photosensitizing substances. Psoralen is an example of photosensitizing substances.
The phototherapeutical apparatus is also effective for the prevention of inflammatory diseases or hyperproliferative diseases. In these embodiments of the method ultraviolet phototherapy is applied before the appearance of clinical symptoms of the disease.
For a more complete understanding of the present invention and for further features and advantages, reference is now made to the following description taken in conjunction with the accompanying drawings.
Embodiments of the present invention and their advantages are best understood by referring to
The Phototherapeutical Apparatus
The phototherapeutical apparatus, according to embodiments of the present invention is suited for the treatment and prevention of common inflammatory diseases of the body. In some applications the phototherapeutical apparatus is used for the treatment and prevention of the diseases of a nasal mucous membrane and paranasal sinuses such as allergic rhinitis (hay fever), vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis (inflammation in the paranasal sinuses), or nasal polyps with ultraviolet light. In other applications the phototherapeutical apparatus is used for the treatment and prevention of the diseases of a mouth cavity, a throat, an esophagus, a stomach, a small intestine, a large intestine, a gastrointestinal tract, a rectum, an ear, a trachea, a urogenital tract, a portio, a uterus, and a conjunctiva.
In some embodiments ultraviolet light source 1 generates a continuous ultraviolet light, in others a slowly oscillating ultraviolet light. For example, in some embodiments the frequency of oscillations can be below about 10 Hertz. In various embodiments the continuous ultraviolet light and slowly oscillating ultraviolet light will be jointly referred to as quasi-continuous ultraviolet light.
Ultraviolet light source 1 can be, for example, a monochromatic light source or a multiwavelength light source.
A variety of monochromatic light sources, such as lasers, can be used as ultraviolet light source 1, among others xenon chloride laser, nitrogen laser, frequency multiplied Nd:YAG laser, any solid state laser, xenon fluoride excimer laser, any type of UV diode lasers or other lasers emitting light in the UV spectrum. Multiwavelength ultraviolet light sources include, for example, discharge lamps, arc lamps filled with xenon, mercury vapour, xenon and mercury vapour, fluorescent lamps, and UV light emitting diodes (UV-LEDs).
The generated ultraviolet light can have a wavelength in the ultraviolet-B (280 nm-320 nm) and ultraviolet-A (320 nm-400 nm) part of the spectrum.
The volume of the discharge in quartz bulb 12 varies in the range of about 1 mm3 to about tenth of mm3. In some embodiments the discharge volume is positioned approximately in the focus of concave mirror 9, so concave mirror 9 can efficiently focus the emitted ultraviolet light onto focusing lens 15.
In some embodiments a targeting light source 18 is employed to guide and assist the application of the ultraviolet light to the intended tissue surface, as in some embodiments the ultraviolet light beam itself may have no component in the visible spectrum. Targeting light source 18 can be, for example, a HeNe laser or a light diode emitting red light or that of any other colour. The light of targeting light source 18 also passes through dichroic mirror 16, so the targeting light also enters optical guidance system 4 through lens system 17. In some embodiments optical guidance system 4 is also applicable to guide back reflected light, reflected from the site of application. The reflected light passes dichroic mirror 16 and can be detected through an observing optical device 19 to assist the application of the phototherapeutical device.
Optical guidance system 4 can be, for example, an optical cable or arm suitable to guide ultraviolet light. The optical cable or arm can be formed of any one of a large number of known suitable materials, among others quartz glass or capillary tubes filled with a liquid capable of guiding ultraviolet light, wherein the internal surface of the capillary tubes are covered with ultraviolet reflecting material. The diameter of the optical cable can be between about 1 micron and about 10 mm. In some embodiments optical guidance system 4 also performs the spectral filtering of ultraviolet light beam 2.
In the embodiment of
In various embodiments external illuminating light sources are applied to illuminate the tissue area to be treated.
In order to illuminate the tissue surface to be treated, a illuminating light is provided by illuminating light source 27. The generated illuminating light is guided through lens 41 into illuminating optical cable 42. Illuminating optical cable 42 can be also integrated into flexible endoscope 37. The illuminating light illuminates the tissue surface to be treated through patient interface 5.
Light reflected from the illuminated tissue surface is conducted back from the illuminated tissue surface via image processing optical cable 38, which can be integrated into flexible endoscope 37 as well. Image processing optical cable 38 is coupled into image processing unit 39 to facilitate visual control of the application of the phototherapeutical apparatus.
In some embodiments optical guidance system 4 can be rotated within flexible endoscope 37 by positioning unit 40, so that the direction of ultraviolet light beam 2 emitted through patient interface 5 can be modified. In other embodiments flexible endoscope 37 itself can be rotated by positioning unit 40. These embodiments are useful for the treatment of various body cavities, for example, a larynx, a digestive canal, and urogenital organs.
Some embodiments for the circular and the spot treatment of tissue surfaces may include a Panoramic Annular Lens (PAL) optical system. A PAL system, transparent to the ultraviolet light can be included into circular applicator head 34 and spot applicator head 35. Including a PAL optical system can be helpful for simultaneous treatment of tissue surfaces and optical image processing.
According to embodiments of the invention, a phototherapeutical method 200 is described for the treatment and prevention of inflammatory and hyperproliferative diseases of body cavities, more particularly for the treatment and prevention of common inflammatory diseases of the nasal mucous membrane and paranasal sinuses, including allergic rhinitis (hay fever), vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis (inflammation in the paranasal sinuses), and for the treatment and prevention of hyperproliferative diseases, including nasal polyps (a frequent benign hyperproliferative lesion in chronic inflammatory conditions of the nasal mucous membrane).
Phototherapeutical method 200 is based on the inventor's research results, which showed that the application of ultraviolet light on tissue surfaces in body cavities decreases the number and the activity of inflammatory cells (mast cells, eosinophils, and lymphocytes) responsible for the mediator release and synthesis in the mucous membrane, and thereby it reduces the clinical symptoms of inflammatory, hyperproliferative, and allergic diseases. This effect of the ultraviolet light may be partly due to apoptosis induction.
Embodiments of phototherapeutical method 200 can be practiced on various body cavities. These body cavities include: nasal cavity, paranasal sinus, mouth cavity, throat, esophagus, stomach, small intestine, large intestine, gastrointestinal tract, rectum, ear, trachea, urogenital tract, portio, uterus, and conjunctiva. It is understood that all these embodiments belong to the scope of the application.
In step 204 some embodiments of phototherapeutical apparatus 100 include essentially monochromatic ultraviolet light sources, other embodiments include multiwavelength ultraviolet light sources. In some embodiments of phototherapeutical apparatus 100 the monochromatic light source was a xenon chloride excimer laser with a wavelength of 308 nm. It was found that a 308 nm xenon chloride laser induces dose and time-dependent T-cell apoptosis. Further, it was found that applying a xenon chloride laser induces the apoptosis of T-cells at a significantly higher rate than applying a narrow-band UVB (NB-UVB) light.
Other embodiments of phototherapeutical apparatus 100 utilize other monochromatic ultraviolet light sources, for example, a nitrogen laser, a frequency multiplied Nd-YAG laser, a xenon fluoride excimer laser, any type of ultraviolet diode lasers, or any other laser, which emits light in the ultraviolet spectrum.
Yet other embodiments include multiple wavelengths ultraviolet light sources, for example, discharge lamps and arc lamps. Each of these lamps can be filled, for example, with xenon, mercury vapour, and a mixture of xenon and mercury vapour. Other embodiments include fluorescent lamps, NB-UVB lamps, ultraviolet light emitting diodes (UV-LEDs), and dye lasers.
In step 206 a preparation for the treatment by phototherapeutical method 200 is performed. The preparation can include determining a light threshold of the particular patient on a part of the patient's skin, which was not recently exposed to sunlight. One measure of a light threshold is the Minimal Erythema Dose (MED). The MED is the smallest dose of ultraviolet light, which causes erythema on the patient's previously unexposed skin after 24 hours. The MED is then used to determine the value of the first dose, applied to the area to be treated.
The preparation can further include selecting a suitable patient interface 5 for practicing phototherapeutical method 200. This choice depends, for example, on the location of the area of the tissue surface to be treated and the anatomy of the body cavity of the patient.
In step 212 ultraviolet light is generated by ultraviolet light source 1.
In step 216 the generated ultraviolet light is coupled into patient interface 5 through optical guidance system 4.
In step 220 the generated ultraviolet light is applied by patient interface 5 to a tissue surface of a body cavity. In some embodiments of the method, the previously determined MED value is used to determine the first dose, applied to the tissue surface to be treated.
In some embodiments of the method, step 220 includes inserting patient interface 5 at least partially into the body cavity. Patient interface 5 is inserted at the distal end.
In some embodiments of step 220, where the tissue surface is the nasal mucous membrane, an ultraviolet light was applied through patient interface 5 with a dose between about 20 mJ/cm2 and about 1000 mJ/cm2, depending on the type of the ultraviolet light source itself. The treatment with ultraviolet light can be repeated one or more times per week. The repeated application of ultraviolet light can be performed with the same dose or with increasing doses, depending on the patient's tolerance and on the improvements of the clinical symptoms.
Research indicated that the clinical symptoms of the treated nasal mucous membrane improved considerably with the treatment. These symptoms include nasal blockage, nasal itch, nose running, sneezing, and itching of the palate in patients with allergic rhinitis.
Similar improvements were observed in the clinical symptoms of vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis, and in the sizes of nasal polyps after treatment with phototherapeutical method 200. The clinical symptoms decreased considerably after the treatment.
In some embodiments the preparation of step 206 includes increasing the efficacy of phototherapeutical method 200 by administering photosensitizing substances before the phototherapy. Sometimes this method is referred to as photochemotherapy. An example for photosensitizing substances is psoralens, including 5-methoxypsoralen, 8-methoxypsoralen, and trimethoxypsoralen. These materials can be used in concentrations between about 0.0005% and about 0.5%, furthermore they can be applied in creams or in solutions.
When a photosensitizing substance is applied in step 206, the minimal phototoxicitiy dosis (MPD) can be measured on a part of the patient's skin, which was not exposed to sunlight before starting the therapy. The MPD is the smallest ultraviolet dose, which induces erythema on a previously unexposed photosensitized skin after 72 hours.
In step 220 ultraviolet light is applied to the nasal mucous membrane, which was photosensitized with the same photosensitizing substance as in step 206. The application can be started with a dose about 0.1×MPD to about 5.0×MPD, depending on the severity of the symptoms of the patient. During repeated applications in some embodiments the dose remains approximately constant. In other embodiments the dose is increased depending on the patient's tolerance. Step 220 can be repeated once or several times per week.
Research showed that practicing photochemotherapy through steps 206-220 by applying photosensitizing materials inhibits rapidly and effectively the clinical symptoms of hay fever, including nasal blockage, nasal itch, nose running, sneezing and itching of the palate.
Similar improvements are observed in the clinical symptoms of vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis, and the sizes of nasal polyps considerably decreased after ultraviolet photochemotherapy.
Phototherapeutical method 200 is also suitable for the prevention of inflammatory and hyperproliferative diseases of body cavities. For example, in the case of seasonal allergic rhinitis phototherapeutical method 200 can be started before the appearance of the clinical symptoms. In this embodiment, the prevention is also based on the minimal erythema dose (MED) of the patient and can be administered once or several times per week.
Similarly, phototherapeutical method 200 with photochemotherapy is also suitable for the prevention of the clinical symptoms of patients with seasonal allergic rhinitis. The treatment can be started before the appearance of the symptoms. For prevention, phototherapeutical method 200 can be started with doses between 0.1×MPD and 2×MPD, depending on the severity of the allergy. The treatment can be administered once or several times per week depending on the tolerance of the patient.
Finally it is noted that the application of phototherapeutical method 200 is significantly cheaper than presently practiced drug based treatments.
Potential Side Effects
Ultraviolet light might facilitate the appearance of viral and bacterial infections on the treated areas because of its immunosuppressive effect. This effect is similar to the effect of topical corticosteroides. However, the likelihood for these infections is lower than that of the presently used local immuno-suppressive preparations, because ultraviolet light also has a direct microbicidal effect (Folwaczny M, Liesenhoff T, Lehn N, Horch H H: Bactericidal action of 308 nm excimer-laser radiation: an in vitro investigation. J Endodontics, 24: 781-785, 1998). Furthermore, ultraviolet light also increases the direct microbicidal activity of epithelial cells (Csat M, Kenderessy Sz A, Dobozy A: Enhancement of Candida albicans killing activity of separated human epidermal cells by ultraviolet radiation. Br J Dermatol 116: 469-475, 1987).
Further, it is well known that repeated irradiation by ultraviolet light in high doses has carcinogenic potency. However, the carcinogenic effect of ultraviolet light is connected with the cumulative dose of the ultraviolet light over years. Since the irradiation doses administered during phototherapeutical method 200 are much lower than the known carcenogenically significant doses, the risk of carcinogenesis is barely increased by the present phototherapeutical method 200.
Practicing phototherapeutical method 200 with phototherapeutical apparatus 100 is further illustrated through the following examples.
The symptoms of a patient suffering from ragweed-induced hay fever 10 years ago did not respond to the used antihistamine and topical corticosteroid nasal drops satisfactorily. At examination the patient complained of severe nasal blockage, nasal itching, nose running, frequent sneezing and itching of the nasal palate. On an area of the back of the patient, which was not recently exposed to sunlight, the minimal erythema dosis (MED) was determined to be about 200 mJ/cm2, using a 308 nm xenon chloride laser as ultraviolet light source. One day later the phototherapy of the nasal mucous membrane was started. For this purpose ultraviolet light beam 2 of ultraviolet light source 1 was directed by optical focusing into optical guidance system 4. Optical guidance system 4 was an optical cable made of quartz and it had a diameter of 1.6 mm. The optical cable was connected to patient interface 5 of the type shown in
The treatment was controlled visually under protection of ultraviolet protecting glasses using the visible light beam of illuminating light source 27 mounted into handgrip 20 of patient interface 5. The complete time of a treatment was 5 minutes, including the time necessary to change the position of patient interface 5. The treatment did not cause any complaint by the patient. This treatment was repeated two times per week using the same phototherapeutical apparatus, but the irradiation dose was increased by 50 mJ/cm2 weekly. After the second treatment the symptoms and complaints of the patient decreased to a large extent and in the third week after the sixth treatment the patient was completely free of symptoms. The treatment was stopped and no recurrence was observed. The treatment was quick and caused no complaint from the patient. The patient did not receive any drugs during the treatment. In comparison to the therapies used earlier, phototherapy was found to be more efficacious by the patient.
Phototherapeutical treatment was also performed on patients with perennial allergic rhinitis, which was induced by house dust mite and whose treatment with antihistamine and local steroids proved to be ineffective. The phototherapy was performed with xenon chloride excimer laser of wavelength of 308 nm.
The MED was measured for each patient and phototherapy was started with 0.5×MED doses. Circular applicator head 34 for cylindrically symmetric treatment was inserted into the meatus nasi inferior area of the nasal cavity for the treatment, then a cylindrically symmetric irradiation was administered onto the tissue surface with the xenon chloride laser. The length of impulses was 15 ns, the frequency of irradiation was 10 Hz. The energy density of each impulse was 2 mJ/cm2. The administering of the dose of 100 mJ/cm2 took 5 seconds. Circular applicator 34 was then inserted into middle and thereafter into the upper part of the nasal cavity and the treatment was repeated in these positions in the same way. The treatment of the right and left nasal cavities took up approximately 2 minutes. The treatment was repeated with the same doses two times per week. After the eighth treatment the clinical symptoms of the hay fever improved considerably at each patient, whereas no side effects were observed.
The severe symptoms of a patient suffering from ragweed-induced hay fever did not improved satisfactorily after using antihistamines and topical corticosteroid nasal drops. At examination the symptoms (nasal blockage, nasal itching, nose running, frequent sneezing, and itching of the nasal palate) of the patient were severe, therefore phototherapeutical method 200 was performed with photochemotherapy. The minimal phototoxicity dose was measured on the forearm of the patient not exposed to sunlight. Ultraviolet light source 1 of the type shown in
Patient interface 5 was brought into contact with the nasal mucous membrane altogether in eight positions in each nostril. The treatment of the nostrils took approximately 3 minutes and caused no complaints from the patient. This photochemotherapy was repeated once per week. The symptoms of the patient improved considerably after the second treatment already and after the third treatment the patient was completely free of symptoms. The treatment was stopped after the fourth treatment. After the therapy the symptoms of the patient did not return.
A patient had a large polyp in the left nostril, which did not improve after administering local corticosteroids. The polyp caused chronic sinusitis, therefore phototherapeutical method 200 was performed with a xenon chloride laser. The minimal erythema dose (MED) was determined on the back of the patient, which proved to be 250 mJ/cm2. For the purpose of phototherapy ultraviolet light beam 2 of wavelength of 308 nm was coupled into optical guidance system 4 after focusing. Optical guidance system 4 was a quartz ultraviolet light conducting cable of diameter 0.5 mm. Optical guidance system coupled ultraviolet light beam 2 into patient interface 5 of the type shown in
In a patient with chronic rhinosinusitis with unknown origin different drugs, including antihistamines, corticosteroids, and antibiotics were used, but proved to be ineffective. Therefore, phototherapeutical method 200 was administered. Ultraviolet light source 1 of the type shown in
Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions, and alterations can be made therein without departing from the spirit and scope of the invention as defined by the appended claims. That is, the discussion included in this application is intended to serve as a basic description. It should be understood that the specific discussion may not explicitly describe all embodiments possible; many alternatives are implicit. It also may not fully explain the generic nature of the invention and may not explicitly show how each feature or element can actually be representative of a broader function or of a great variety of alternative or equivalent elements. Again, these are implicitly included in this disclosure. Where the invention is described in device-oriented terminology, each element of the device implicitly performs a function. Neither the description nor the terminology is intended to limit the scope of the claims.
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|International Classification||A61N5/067, A61N5/06, A61B18/20|
|Cooperative Classification||A61N2005/0661, A61N2005/0607, A61N5/0603, A61N2005/067, A61N2005/0606, A61N5/0601, A61N2005/0605, A61N5/062, A61N2005/0644, A61N2005/0608, A61N2005/0611, A61N2005/0609|