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of allergic rhinitisExpert Rev. Med. Devices
7(1), 21–26 (2010)
Allergic rhinitis, although not life threatening, signiﬁcantly affects the quality of the patient’s
daily life. The three major steps in the treatment of the condition are avoidance of allergens,
treatment of symptoms (in particular, antihistaminics and topical nasal corticosteroids) and
speciﬁc immunotherapy. Avoidance of the allergen is usually not possible and symptom relief
is often limited, despite the availability of a number of pharmacological options. Speciﬁc
immunotherapy demands a high level of cooperation on the part of the patient for at least
3 years. Endonasal phototherapy with the Rhinolight® device (Rhinolight Ltd, Szeged, Hungary)
for the treatment of immunoglobulin E-mediated allergic rhinitis is a new option that utilizes the immunosuppressive effects of UV radiation. The method directs a combination of UV-B (5%), UV-A (25%) and visible light (70%) into the nasal cavity, and its effectiveness has been demonstrated in one double-blind, placebo-controlled study. The results of additional studies have been presented at various medical conferences and in abstracts. Reports in the literature conﬁrm that phototherapy is a well-established and successful treatment of atopic dermatitis and other skin diseases.
allergic rhinitis • phototherapy • Rhinolight® • ultraviolet therapy
Allergies represent one of the greatest health
The severity of the symptoms are to be deﬁned
problems in modern societies . A tentative on the basis of their intensity and their effect on estimate of the prevalence of allergic rhinitis the patient’s quality of life:(AR) suggests a ﬁgure of 500 million suffer-
• Mild: symptoms are present but do not impair
ers worldwide . This would make AR one
of the most common allergic diseases in the world, with increasing prevalence and often • Moderate/severe: symptoms are present and far-reaching consequences for quality of life,
since it also reduces the patient’s efﬁciency
In the Allergic Rhinitis and its Impact on
and leads to labor and productivity losses [3,4].
Asthma (ARIA) updates, a joint effort of the
The condition, therefore, has a signiﬁcant WHO and the Global Allergy and Asthma socioeconomic impact.
Exposure of the nasal mucosa to various aller-
gic stimuli can cause rhinitis. AR is deﬁned clini-
treatment for the moderate-to-severe intermit-
cally as a symptomatic disease of the nose caused tent and persistent forms of AR . Apart from by a speciﬁc type of IgE-mediated inﬂammation allergen avoidance, SIT is the sole causal thera-of the nasal mucosa triggered by exposure to an peutic concept for the treatment of IgE-mediated allergen. It is classiﬁed into a seasonal, a peren-
nial and an occupational form. The WHO has
proposed a classiﬁcation based on the duration Role of immunotherapy in
of the symptoms :
• Intermittent: less than 4 days per week, or less The effectiveness of SIT, both in the sub-
cutaneous (SCIT) and sublingual (SLIT) application forms for the treatment of AR,
• Persistent: more than 4 days per week, or has been conﬁrmed in double-blind, random-
ized, placebo-controlled studies and in various
Special Report Brehmer
meta-analyses [5,6]. Such studies have shown a high degree of the risk of a serious reaction to SIT is low, the incidence of such effectiveness against tree-, grass- and cereal-pollen allergies, as reactions has increased since the introduction of standardized and well as against those caused by mugwort and ragweed. In the more potent extracts . New routes of application, for exam-case of perennial allergies, a therapeutic effect has been shown ple, intralymphatic injection of allergens, are currently being against house dust mites and animal dander [7,8]. Worldwide, SIT investigated .
for the treatment of allergic diseases is very common outside the
USA and the UK. In an ofﬁcial report published in 2007, it was Rhinophototherapy
stated that in Great Britain, immunotherapy was not used to its Recently, a rhinophototherapy device, Rhinolight® (Rhinolight
full potential, the reason being partly historical – when early types Ltd, Szeged, Hungary), enabling the application of radiation
of immunotherapy were administered, a number of patients had comprising a combination of UV-B (5%), UV-A (25%) and vis-
suffered anaphylactic shock .
ible light (VIS; 70%) to the nasal mucosa in AR patients has
The immunological mechanisms of SIT are not fully known. been developed. The utilization of UV radiation in medicine
SIT induces clinical and immunological tolerance to the allergens is nothing new and was ﬁrst employed at the beginning of the employed, with a long-term effect that persists beyond the dura-
19th Century, when Finsen successfully applied phototherapy to
tion of treatment. The development of immunological tolerance is heal lupus vulgaris . Since then, phototherapy has been used an active response on the part of the immune system, and involves in various modalities (broadband UV-B [290–320 nm], narrow-a complex interaction between the allergen administered and the band UV-B [311 ± 2 nm], 308 nm UV-B excimer laser, UV-A immune system. The success of the treatment is dependent on the [320–400 nm], photosensitizer and UV-A [PUVA], combined quality of the allergen vaccine (immunological activity) and the UV-A/UV-B, high-dose UV-A1 [340–400 nm] and high-dose duration of its application (the total dose of the allergen extract, VIS [400–800 nm]) in the ﬁeld of dermatology, for example, to administered for at least 3 years). Since the allergen extracts dif-
successfully treat atopic dermatitis and numerous skin diseases .
fer in terms of the manufacturing process, each manufacturer UV radiation has a range of biological effects – including local has its own in-house reference preparation (IHRP) to determine and systemic immunosuppression and immunomodulation – but the immunological activity; they cannot be compared directly.
also undesired effects, such as induction of premature ageing of
According to the present state of our knowledge, the major the skin and skin cancer . The immunosuppressive effect of
target cells of SCIT are T lymphocytes. Their function is inhib-
UV light is due to the induction of apoptosis [27,28], its inﬂuence
ited by the activation of regulatory CD4+ T cells, which produce on antigen presentation  and the suppression of surface mol-IL-10, TGF-E and mediate tolerance, and by the induction of ecules  that play a major role in antigen presentation, and the anergia-reduced responsiveness with decreasing cytokine pro-
induction of immunosuppressive mediators [31,32].
duction, and proliferation after stimulation via the T-cell recep-
The working group headed by Kemeny showed that application
tor [10–12]. The result, over the long term, is a shift in the immune of the 308-nm UV-B excimer laser in the treatment of AR leads response: a dominant TH2 response (e.g., IL-4, IL-5 and IL-13) to a signiﬁcant improvement in total nasal symptom score (TNS), is replaced by an enhanced TH1 response (IFN-J) [12,13]. but the wheal induced by the skin prick test was inhibited only Secondarily, the immunoglobulin production of the B lympho-
at erythematous doses . A study by the same working group
cytes changes with induction of the allergen-speciﬁc IgG and, in demonstrated that irradiation with a combination of UV-B (5%),
particular, IgG4 production, and possibly a slower reduction in UV-A (25%) and VIS (70%) at suberythematous doses achieved
allergen-speciﬁc IgE production. The function of effector cells, a similar inhibitory effect on immediate-type skin reaction, as
such as mast cells, and basophilic leukocytes or eosinophilic with higher erythematous doses of UVB alone . These ﬁnd-
granulocytes, is inhibited . The immunological mechanisms ings prompted a randomized, double-blind study in 49 patients
of SLIT seem to be similar to those of SCIT – with induction of with hay fever . By comparison with baseline, the individual
tolerance via antigen-presenting cells (APCs) of the oral mucosa scores decreased signiﬁcantly for sneezing, rhinorrhea and nasal
playing a central role [14,15]. Preserving contact of the allergen itching, but not for nasal obstruction.
with the oral mucosa would appear to be critical for the efﬁcacy
of SLIT . In comparison with SCIT, administration of an at Technique
least 50- to 100-fold subcutaneous dose is recommended for Treatment is applied for 2–3 min, three times a week for 2 con-
SLIT . However, for SIT to be effective, cooperation on the secutive weeks in the seated patient during the pollen season.
part of the patient is necessary – he/she must undergo regu-
During treatment, the patient experiences neither a sensation of
lar, usually monthly, injections in the case of SCIT, and daily heat nor pain. A total of six treatments are applied during the 2 administration of the allergen extract when SLIT is employed weeks but not more than four in 1 week. During a session, both – and this regimen is generally maintained for a minimum of the patient and the physician must wear glasses that protect their 3 years. The literature reports compliance ﬁgures of between eyes against UV light. The ﬁrst treatment is frequently followed 44 and 88% for SCIT, and between 76 and 97% for SLIT [18,19].
by deterioration in symptoms. Prior to each session, the patient is
The risk of an anaphylactic reaction to SIT is feared by both required to clear his nose. Before phototherapy is begun, the endo-
physicians and patients alike. Fatalities and serious side effects nasal mucosa is treated with decongestant nose drops to ensure have been reported both for SCIT and SLIT [20,21]. Although that the maximal surface area of the mucosa is irradiated. A nasal
Expert Rev. Med. Devices
Endonasal phototherapy with Rhinolight® in allergic rhinitis
adapter screwed to a special device is introduced into the nasal group comprising 34 patients was formed. The parameters inves-vestibule. This device is connected to the equipment by a light-
tigated were the TNS and the Rhinoconjunctivitis Quality of Life
conducting cable. During irradiation, the physician gently rotates Questionnaire (RQLQ) . The results showed a statistically the device in order to avoid the radiation being concentrated on a signiﬁcant improvement in all the variables in the phototherapy single point. For the duration of the treatment, the nasal mucosa group. In all cases, endonasal phototherapy was well tolerated, is treated with emollients.
the sole side effect being dryness of the nasal mucosa during the
treatment, which, however, responded well to emollients. Not a
Efﬁcacy & safety
single case of serious side effects occurred.
The effectiveness of endonasal phototherapy has been investi-
It has been shown in vivo
and in vitro
gated in seven studies involving 537 patients. In a randomized, photo therapy actively suppresses the effector phase of AR at controlled, double-blind study, 49 patients with ragweed-induced multiple points:hay fever who were unresponsive to anti-allergy drugs were evalu-
• Reduction of the antigen-presenting capacity of APCs
ated . The two groups did not differ in terms of their anthro-pometric data, disease duration or symptoms score. In compari-
• Induction of apoptosis of immune cells (dendritic cells, T-cells,
son with baseline, this study showed a signiﬁcant improvement
in the clinical symptoms of sneezing (p < 0.016), rhinorrhea • Inhibition of synthesis and release of proinflammatory
(p < 0.007), nasal itching (p < 0.014) and TNS (p < 0.004)
mediators from eosinophils, mast cells, basophils and T-cells
in the treatment group. None of the scores improved signiﬁ-cantly in the control group. Examination of nasal lavage samples
The major molecular target for UV-induced immuno-
showed effects on eosinophils and inﬂammatory mediators. The suppression is UV-induced DNA damage . It is this very point authors found signiﬁcantly lower concentrations of eosinophils, that prompts criticism of endonasal phototherapy, expressed as a eosinophilic cationic protein and IL-5 in the treatment group. fear that endonasal phototherapy might have a carcinogenic effect In a smaller, double-blind, placebo-controlled study, 67% of the on the nasal mucosa. A study has investigated the extent of DNA treated patients experienced a signiﬁcant improvement in symp-
damage prior to and following a 2-week endonasal phototherapy
toms . In an open, multicentric study of 70 ragweed patients, session . The chemical evaluation was performed in the labo-the overall efﬁcacy assessment showed a signiﬁcant inhibition of ratory and immunohistochemical investigations conducted on the clinical symptoms in 90% of the patients . Another study the nasal cytology samples prior to the initiation of treatment, involving 37 patients (15 with intermittent and 22 with persistent and immediately after the ﬁnal session, 10 days thereafter and AR) provided similar results .
then 2 months after the last application. A signiﬁcant increase in
In a study including 59 patients with a history of at least 2 years DNA damage was found in the mucosa immediately following the
of ragweed-induced AR treated with endonasal phototherapy, 38 last therapeutic session. The damage had decreased signiﬁcantly (64%) patients experienced a decrease of more than 50% in the 10 days later and was comparable with baseline: 2 months later, average change in the TNS .
the ﬁndings were comparable with those seen in healthy control
In an open study, the effectiveness of endonasal photo therapy persons. Mitchell et al
. investigated DNA damage and repair after
was compared with the effect of the antihistamine fexo fenadine a single UV irradiation (combination of UV-C, UV-B, UV-A hydrogen chloride (120 mg) in patients with ragweed AR. TNS and some VIS) of human nasal mucosa in 30 adults . Nasal was decreased signiﬁcantly in the endonasal phototherapy group cytology samples were taken prior to, and immediately after, treat-(p = 0.00003) but no signiﬁcant change was seen in the fexo-
ment, and 24, 48 and 72 h later. DNA damage in samples taken
fenadine hydrogen chloride group . Bella et al
. investigated the immediately after UV irradiation was measured in all subjects and effect of endonasal phototherapy in 243 patients with grass-pollen was signiﬁcantly greater than that at baseline. The DNA damage AR . One group received endonasal phototherapy alone, while at 24, 48, and 72 h showed no signiﬁcant difference compared the other group received, in addition to endonasal phototherapy, a with baseline. In a second investigation in the same study, DNA once-daily oral dose of an antihistamine or a nasal steroid (maxi-
damage to, and repair of, nasal epithelium was evaluated in nasal
mum: 400 μg/day). However, only 75 patients were evaluated. cytology samples before and after nine treatments applied over Nasal symptoms were improved signiﬁcantly in each group. In 3 consecutive weeks. At 1 and 4 weeks after the ﬁnal treatment, the group receiving endonasal phototherapy alone, 6% of the DNA damage had returned to the original baseline level. The patients experienced a worsening of their symptoms compared authors conclude that human nasal mucosa is capable of efﬁciently with 5% in the group receiving phytotherapy and medication. repairing UV-induced DNA damage. Earlier studies performed No change in symptoms was seen in 19% of the phototherapy on bronchial ﬁbroblasts and epithelial cells established DNA versus 8% of the phototherapy plus medication groups. On a repair similar to that seen in human skin ﬁbroblasts, suggesting visual analog scale, 75% of the patients receiving monotherapy that there is no difference in DNA repair mechanisms among indicated an improvement, in comparison with 87% of the group different cell types . Lee et al
. evaluated all prospective and receiving combined treatment. Cingi et al
. prospectively investi-
retrospective studies identiﬁed in Medline between 1966 and June
gated the action of the endonasal phototherapy and its effect on 2002 with a view to estimate the risk of skin cancer associated quality of life in 100 patients with intermittent AR . A control with UV-B phototherapy, but found no increased skin cancer risk
Special Report Brehmer
associated with UV-B phototherapy . In another, more recent, septal deviation or massive nasal polyposis. Phototherapy is also study involving 3867 patients treated with narrow-band UVB contraindicated in acute rhinosinusitis, in the presence of tumors phototherapy, no association was found between narrow band of the nasal mucosa, sinuses or nasopharynx. Prior to the applica-UV-B exposure alone and any skin cancer .
tion of endonasal phototherapy, it is most important to ensure that
The surface area of each nasal cavity per nostril is 20 cm2, and the patient is not taking photosensitizing drugs. Advantages of
UV-A accounts for 25% and UV-B for 5% of the total emission this form of treatment are its good tolerability and repeatability.
energy. Using the treatment protocol for seasonal AR, comprising The application is simple and painless, and possible side effects six sessions, the total treatment time is 930 s. For six treatments, the such as dryness of the nasal mucosa or crusting can readily be cumulated dose of UV-B is 4185 J/m2 and of UV-A, 20925 J/m2. treated by appropriate nasal care.
The average UV exposure of males and females in the southern
Although investigations into the safety of endonasal photo-
hemisphere (e.g., 34° South) varies between 29,000 J/m2 for indoor therapy suggest that UV-induced damage to nasal mucosa is workers and 95,000 J/m2 per year for outdoor workers .
efﬁciently repaired [44–46], a degree of uncertainty remains with
regard to the possibility of cancerogenicity, since long-term inves-
Expert commentary & ﬁve-year view
tigations are still lacking. The author is, therefore, of the opinion
Research into the development of endonasal phototherapy of AR that the number of treatment regimes per patient should be lim-was begun in 1999 by researchers at the dermatological clinic ited to a single regime per year. The equipment has been awarded and the Faculty of Science at the University in Szeged, Hungary.
a Conformité Européene (CE) mark and thus meets the require-
In the meantime, according to the manufacturer of the device, ments of the EU guidelines on health and safety. Since endonasal
endonasal phototherapy is employed in the following 19 coun-
phototherapy is, at present, not performed in the UK, Rhinolight
tries: Hungary, Slovakia, Romania, Serbia, Croatia, Poland, has not been recognized by NICE. Bulgaria, Greece, Austria, Switzerland, the Ukraine, Russia,
Owing to its novelty and some as yet unresolved questions,
Germany, Italy, Portugal, Turkey, Hong Kong, South Korea and endonasal phototherapy should be considered an effective alterna-Japan. Over the last 5 years, approximately 10,000 patients have tive, but not be promoted to, ﬁrst-line therapy for AR. Allergies been treated with this modality worldwide, with half of the treat-
are on the increase worldwide, and there is a need to develop
ments being carried out in Hungary. Endonasal phototherapy treatments that work rapidly on symptoms and do not lose their can readily be performed during the pollen season, does not take effectiveness over time. When long-term studies have conﬁrmed long and relieves the patient of their symptoms. Endonasal photo-
the safety of this form of treatment and the persistence of its
therapy represents an alternative form of treatment in patients effect, endonasal phototherapy will play an important role in the
who refuse medication (e.g., drugs, SCIT or SLIT), who have treatment of AR – as it already does in the ﬁeld of dermatology.
experienced a severe side effect with SCIT or SLIT, in whom
drug treatment produced no, or only inadequate, effects, or who Financial & competing interests disclosure
were unable to undergo SIT owing to contraindications (inad-
The author has no relevant afﬁliations or ﬁnancial involvement with any
equately treated asthma and/or irreversible airway obstruction, organization or entity with a ﬁnancial interest in or ﬁnancial conﬂict with
severe cardiovascular disease, local or systemic treatment with the subject matter or materials discussed in the manuscript. This includes
E-blockers, inadequate compliance, pregnancy, nursing, or they employment, consultancies, honoraria, stock ownership or options, expert
were a competitive athlete). Contraindications for endonasal testimony, grants or patents received or pending, or royalties.
photo therapy include anatomical variations, such as a pronounced
No writing assistance was utilized in the production of this manuscript.
• Allergic rhinitis (AR) is an increasing global health problem, and the costs it incurs are substantial. In the UK, direct NHS costs for the
management of allergic problems are estimated at more than GB£1 billion per annum.
• Untreated AR has a major inﬂuence on a patient’s ability to sleep, their quality of life and cognitive function, and on
• According to the WHO, AR must be considered a risk factor for the development of asthma.
• AR is a symptomatic disorder of the nose induced by IgE-mediated inﬂammation after allergen exposure of the membranes lining
• The backbone of its treatment is avoidance of allergens, use of drugs and speciﬁc immunotherapy.
• The radiotherapy device Rhinolight® is effective agaist AR.
• The application of endonasal phototherapy has, to date, been free from serious side effects.
• Endonasal phototherapy is an effective alternative when speciﬁc immunotherapy is contraindicated or when when antiallergic
medication is not tolerated, associated with side effects or is inadequate.
• Data on long-term efﬁcacy and safety are mandatory. Efforts should be undertaken to re-evaluate those patients who have
• Provided that long-term studies conﬁrm the effectiveness and safety of endonasal phototherapy, it will have an important role to play
Expert Rev. Med. Devices
Endonasal phototherapy with Rhinolight® in allergic rhinitis
12 Jutel M, Pichler WJ, Skrbic D, Urwyler A,
Papers of special note have been highlighted as:
immunotherapy results in decrease of IL-4
sun? J. Am. Acad. Dermatol.
and IL-5 and increase of IFN-J-secretion in
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Special Report Brehmer
Koreck AI, Csoma Z, Bodai L et al.
•• Identiﬁes similar DNA repair in bronchial
Rhinophototherapy: a new therapeutic tool
Rhinophototherapy in grass pollen induced
ﬁbroblasts and epithelial cells as in
for the management of allergic rhinitis.
allergic rhinitis. WAO J.
human skin ﬁbroblasts. The authors
J. Allergy Clin. Immunol.
conclude that DNA repair mechanisms
are equally efﬁcient in all cell types.
•• Describes the efﬁcacy of phototherapy in
Lee E, Koo J, Berger T. UVB phototherapy
phototherapy on quality of life in allergic
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43 Juniper EF, Guyatt GH. Development and
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•• Summarizes the association between
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mucosa in patients with allergic rhinitis.
cell carcinomas, squamous cell carcinomas
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Phototherapy for allergic rhinitis – our
•• Found that nasal mucosa exposed to UV
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light posses the capacity to repair
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Mitchell D, Paniker L, Sanchez G et al.
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•• Demonstrates the capacity of airway
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46 Fornace AJ Jr, Lechner JF, Grafstrom RC,
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Expert Rev. Med. Devices
Proc. Interamer. Soc. Trop. Hort. 47:61-64. Vegetables/Hortalizas - October 2003 Qualidade e Conservação Pós-Colheita de Melão Gália Híbrido 'Arava' Submetido a Aplicações Pré- Colheita de Quelato de Cálcio e Boro Fábio del Monte Cocozza e Adimilson Bosco Chitarra, Universidade Federal de Lavras, Caixa Postal 37, 37200-000 Lavras, MG, Brasil, firstname.lastname@example.org Everardo Ferre
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