Chest
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
First published online on October 1, 2007
Chest, doi:10.1378/chest.07-1410
doi:10.1378/chest.07-1410
(Chest. 2008; 133:123-130)
© 2008 American College of Chest Physicians
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
chest.07-1410v1
133/1/123    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nakagishi, Y.
Right arrow Articles by Kikuchi, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakagishi, Y.
Right arrow Articles by Kikuchi, M.

Photodynamic Therapy for Airway Stenosis in Rabbit Models*

Yoshinori Nakagishi, MD; Yuji Morimoto, MD, PhD; Masanori Fujita, MD, PhD; Noriko Morimoto, MD, PhD; Yuichi Ozeki, MD, PhD; Tadaaki Maehara, MD, PhD and Makoto Kikuchi, PhD

* From the Departments of Medical Engineering (Drs. Nakagishi and Kikuchi), Surgery (Drs. Fujita, Ozeki, and Maehara), and Integrative Physiology and Bio-Nano Medicine (Dr. Y. Morimoto), National Defense Medical College, Tokorozawa, Saitama; and Department of Otolaryngology (Dr. N. Morimoto), National Center for Child Health and Development, Setagaya, Tokyo, Japan.

Correspondence to: Yoshinori Nakagishi, MD, Department of Medical Engineering, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan; e-mail: grd1708{at}ndmc.ac.jp

Abstract

Background: Acquired airway stenosis in childhood is resistant to conventional treatment. We examined whether endoscope-assisted photodynamic therapy (PDT) is effective for airway stenosis in animal models of which the pathophysiologic progressions are similar to those of clinical cases showing rapid deterioration.

Methods: Tracheal mucosa-scraped rabbits were administered IV porfimer sodium (Photofrin; Wyeth K.K., Tokyo, Japan) [2 mg/kg], and the tracheal lesions were irradiated with 630 nm of light emitted from a cylindrical diffuser tip via a transtracheal approach.

Results: Rabbits without PDT (untreated animals) showed dense granulation tissue in the scraped lesion, resulting in airway stenosis complicated with respiratory stridor. PDT ameliorated the degree of airway stenosis (p = 0.008) and reduced respiratory stridor; rabbits that received PDT showed patchy granulation tissue that was only 20 to 30% of the volume of that seen in the untreated animals. Survival time of rabbits that received PDT was significantly prolonged compared with that of untreated animals (p = 0.03).

Conclusions: PDT was effective for airway stenosis in rabbit models. This suggests that PDT has the potential as a new therapeutic method for airway stenosis originating from granulation tissue.

Key Words: bronchoscope • endotracheal intubation • granulation tissue • porfimer sodium

Acquired airway stenosis in the pediatric age group is caused by prolonged endotracheal intubation, long-term tracheotomy, airway burn, trauma, and some systemic diseases.1 Since McDonald and Stocks2 reported prolonged endotracheal intubation as a method of long-term ventilatory support in neonates in 1965, the incidence of acquired tracheal and subglottic stenosis in childhood has increased significantly.3 Studies456 have shown that airway stenosis occurs in 0.7 to 4% of children with prolonged endotracheal intubation. Although various methods such as balloon dilatation, laser vaporization, stent implantation, and surgical procedures have been used for the treatment, an effective therapeutic technique has not been established.7 Pediatric surgical procedures have been generally less successful than those in adults89 and can be sometimes complicated with recurrent stenosis by secondary infection, poor healing, or rescarring.10 In addition, surgical procedures are also very invasive for children. Balloon dilatation, laser vaporization, and stent implantation using a bronchoscope are less invasive than surgical methods, but intractable complications such as perforation, fatal hemorrhage, and movement and breakage of stents often occur, thus causing poor clinical outcomes.1112 Therefore, a more effective and less invasive method for treatment of airway stenosis is needed.

Photodynamic therapy (PDT) is a promising antitumor treatment in which photosensitizers that are excited with light of a specific wavelength lead to photochemical destruction of tumor cells via generation of reactive oxygen species such as singlet oxygen.1314151617 Unlike conventional laser treatments using cytocidal physical effects of high-power lasers,13 PDT requires only a small amount of photoenergy for exciting photochemical reactions and, as a result, PDT can be used to treat lesions preferentially with minimal damage to normal tissue. As well as malignant tumors, proliferative diseases such as retinopathy1819 and arteriosclerosis2021 are thought to be good indications for PDT.

Since some photosensitizers such as porphyrin derivatives tend to accumulate in metabolically activated regions,14151617 these photosensitizers are presumed to accumulate in actively proliferating granulation tissue. In fact, we have confirmed that porfimer sodium (Photofrin; Wyeth K.K.; Tokyo, Japan) accumulated in granulation tissue in our newly established rabbit airway stenosis models more selectively than in other tissues.22 This selective accumulation indicates that PDT has potential as a therapeutic strategy for airway stenosis because the therapeutic effects of PDT are predominantly dependent on the concentration of photosensitizers in the lesions.1314151617 However, PDT can be applied to lesions inside tubular organs by an approach using endoscopes and catheters.232425 In fact, endoscope-assisted PDT is frequently performed for lesions in the bronchus, esophagus, and stomach. For this reason, PDT is also suitable as a therapeutic modality for airway stenosis from the standpoint of a practical approach.

We therefore examined whether PDT is effective for airway stenosis. In this study, we verified the effects of PDT on granulation tissue of our newly established airway stenosis animal model,26 of which the pathophysiologic progression is similar to that seen in clinical cases showing rapid deterioration of airway stenosis. Animals were irradiated via a transtracheal approach after IV administration of porfimer sodium, and then bronchoscopic examination of the lesions was performed.

Materials and Methods

Animals
All animal procedures were conducted in accordance with guidelines published by the National Institutes of Health.27 The study protocol was approved by the Ethics Committee for Laboratory Animals of the National Defense Medical College, Tokorozawa, Japan.

Male Japanese white rabbits (Tokyo Laboratory Animal Science; Tokyo, Japan) weighing 2.5 to 3.5 kg were used for the experiment. The rabbits were each anesthetized IM with 35 mg/kg of ketamine and 5 mg/kg of xylazine.28 To enhance analgesia, 2 mL of 1% lidocaine hydrochloride was injected into the subcutaneous area of the anterior neck. During anesthesia and procedures, all rabbits breathed spontaneously. Animals were maintained under a light environment that had a light/dark cycle every 12 h.

Preparation of Airway Stenosis Models
Rabbit models of airway stenosis were prepared by a previously reported method.26 Briefly, after making a midline skin incision in the anterior neck, the larynx and trachea were exposed. The trachea was incised transversely along the tracheal cartilage with an incised length of two thirds of the circumference. The incision point was located 2 to 3 cm caudal to the bottom edge of the cricoid cartilage. A nylon brush was inserted at the incision point into the trachea in the direction toward the mouth. The tracheal mucosa was then circumferentially scraped by pushing and pulling the brush several times.

PDT
Porfimer sodium was dissolved in a 5% dextrose solution and administered IV (2 mg/kg) to 13 rabbits 4 days after scraping. At 24 h after administration of porfimer sodium, the intratracheal cavity was observed using a bronchoscope (BF Type XP60; Olympus; Tokyo, Japan) under IM anesthesia. A 24-h incubation period was used for two reasons: (1) 24-h incubation has been used in most of the reported porfimer sodium-PDT experiments using animal models29303132; and (2) the metabolic rate of small animals is generally faster than that of humans, suggesting that suitable incubation time is shorter in small animals. Photoirradiation was then performed under bronchoscopic monitoring. Light emitted from a 630-nm continuous-wave diode laser (Ceralas PDT630; CeramOptec; Bonn, Germany) was delivered via a silica fiber with an outer diameter of 0.25 mm. The end of the fiber was coupled to a cylindrical diffuser tip with a length of 20 mm (Fig 1 )33 to illuminate the tracheal lesion circumferentially. The lesion was irradiated for 10 min with an irradiation power of 400 milliwatts, which corresponded to a dose rate of approximately 100 milliwatts per square centimeter in the case of rabbit trachea diameter being 6 to 7 mm.


Figure 1
View larger version (7K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1.. Photograph of cylindrical fiber diffuser. Diffuser tip length is 2 cm.

 
Evaluation of Treatment Effect
Twenty-six airway stenosis models made by scraping tracheal mucosa were classified into two groups: a PDT group (13 rabbits) and a control (untreated) group (13 rabbits). Rabbits in the PDT group were treated for airway stenosis with PDT described above, and those in the control group were not provided any treatment, including PDT. Bronchoscopic examination was repeatedly performed to observe the status of tracheal stenosis under IM anesthesia. We evaluated the degree of tracheal stenosis based on the luminal area of the tracheal cavity under bronchoscopic examination and classified the degree of tracheal stenosis into four grades: grade 1, < 25%; grade 2, 25 to 50%; grade 3, 50 to 75%; and grade 4, ≥ 75%. PDT was performed at 5 days after scraping, corresponding to day 0. Survival of animals was monitored, and the larynx and trachea were excised when rabbits died during the observation period. The excised tissue was processed by the procedure of standard hematoxylin-eosin staining and observed under a microscope.

Statistical Analysis
Data are expressed as mean ± SD and were analyzed by Wilcoxon t test or Mann-Whitney U test. A survival curve was obtained by the Kaplan-Meier method and analyzed by the log-rank test; p < 0.05 was considered statistically significant.

Results

Systemic Condition of Animals at 4 Days After Scraping Tracheal Mucosa
Changes in body weight and degree of respiratory stridor at 4 days after scraping of each rabbit are shown in Table 1 . Four days after the scraping operation corresponded to the date when the animals in the PDT group were administered porfimer sodium. The average body weights at the time of the scraping operation in the PDT and control groups were 3.0 ± 0.2 kg and 2.9 ± 0.2 kg, respectively, indicating no significant difference between the two groups. There was also no significant difference in weight loss due to stress from the scraping operation: the weight losses at 4 days after scraping in the PDT and control groups were 0.16 ± 0.11 kg and 0.26 ± 0.13 kg, respectively. Respiratory stridor was heard in all of the rabbits 4 days after scraping, but there was no significant difference between the degrees of stridor of rabbits in the PDT and control groups.


View this table:
[in this window]
[in a new window]

  		Table 1.. Summary of Characteristics of Rabbits With Scraped Tracheas

 
Evaluation of Airway Stenosis at 5 Days After Scraping Trachea Mucosa or Later
Bronchoscopic examination showed that tracheal stenosis was established in all of the 26 rabbits at 5 days after scraping, and there was also no significant difference between degrees of stenoses in rabbits in the PDT and control groups (Table 1). After that, the rabbits in the control group had progressive stridor and progressive tracheal stenosis (Fig 2 , top, A). Due to the respiratory disturbance, general conditions of the control rabbits gradually became worse, and half of them died by day 8 and all of them died by day 17 (Fig 3 ). In the PDT group, tracheal lesions were treated with PDT 5 days after scraping (day 0). One of the rabbits in the PDT group was injured in the tracheal membrane due to bronchoscope tip manipulation, resulting in death caused by bleeding 2 h after PDT, and this the animal was excluded from further analysis. The remaining 12 animals in the PDT group showed no PDT-associated complications. PDT resulted in an improvement in the degree of airway stenosis (p = 0.008) and amelioration of respiratory stridor (Tables 1, 2 ). Survival time in the PDT group was significantly prolonged compared to that in the control group (p = 0.03) [Fig 3]: median survival time points (± SE) in the PDT and control groups were day 13 (± 0.8) and day 8 (± 3.0), respectively. Two rabbits in the PDT group were alive even on day 120. Typical time-lapse bronchoscopic views of the intratracheal cavity of a PDT-treated rabbit are shown in Figure 2, bottom, B. Compared with the state of the lesion before PDT, tracheal stenosis caused by granulation tissue was improved on day 6 in spite of residual mild redness and edema of the tracheal mucosa. On day 13, remarkable improvement of tracheal stenosis was seen and the tracheal mucosa no longer showed redness and edema. Although some cases in the PDT group had redness and edema of the nonscraped tracheal mucosa that was located in a region caudal to the trachea incision line, these lesions had almost disappeared by about day 10 (data not shown).


Figure 2
View larger version (22K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2.. Bronchoscopic views of the intratracheal cavities of untreated rabbit 4 in the control group (top, A) and a rabbit that received PDT (rabbit 1 in the PDT group) [bottom, B].

 

Figure 3
View larger version (8K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3.. Survival curves of the examined animals. There is a significant difference between the survival times in the PDT and control groups (p = 0.03). Censored case is shown by a cross.

 

View this table:
[in this window]
[in a new window]

  		Table 2.. Change of Degree of Tracheal Stenosis*

 
Figure 4 shows histologic photomicrographs of the trachea. In the control group, dense granulation tissue composed of proliferating fibroblasts and thickened collagen fibers was seen in the scraped lesions, implying that submucosal tissue hypertrophy was the primary cause of the tracheal stenosis. These pathologic features were seen in the entire area of the scraped lesion, in which normal submucosal tissue was scarcely detected. However, in the PDT group granulation tissue formation was rarely seen in the scraped lesion, which showed few fibroblasts and collagen fibers. The remaining granulation tissue was patchy in distribution over the lesion. Most of the patchy granulations were located in deep layers of the trachea rather than superficial layers. Other than the patchy granulation, interstitial infiltration of inflammatory cells and some vacuole formations were observed in the scraped lesions in the PDT group. These pathological findings were seen in all of the rabbits that received PDT.


Figure 4
View larger version (63K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4.. Photomicrographs of the trachea in rabbits in the PDT group that died on day 6 (top left, A, and top right, B) and day 19 (lower center, left, E, and lower center, right, F) and untreated rabbits that died on day 6 (upper center, left, C, and upper center, right, D) and day 17 (bottom left, G, and bottom right, H). Cross-sectioned views are shown of the trachea (left column) and high-powered photomicrographs (right column). Scale bar = 0.1 mm.

 
Discussion

In this study, we performed PDT in airway stenosis rabbit models using transtracheal irradiation under bronchoscopic monitoring. This therapeutic modality succeeded in ameliorating airway stenosis caused by granulation tissue and in alleviating respiratory stridor. The survival time of rabbits in the PDT group was extended significantly compared with that of rabbits in the untreated group. Pathohistologic examination in the stenosis area of the rabbits that received PDT showed disappearance or decrease in numbers of fibroblasts and collagen fibers, resulting in suppression of fibrosis. Infiltration of inflammatory cells was also observed after PDT. In addition, some vacuole formations and interfibrous gaps were seen in the lesions of rabbits that received PDT. PDT is known to induce necrosis and apoptosis, followed by a decrease in number of cells and activation of an inflammatory response. As a result, cell density in the treated tissue is reduced, thus resulting in the formation of interstitial gaps.152534 In this study, we performed PDT in airway stenosis rabbit models at an early date (5 days) after scraping tracheal mucosa. This is the time of highest metabolic activity, and it does not reflect the more common clinical scenario: mature granulation tissue months or years after the injury. However, even in this early phase, the present animal model showed remarkable granulation tissue progression responsible for stridor and airway stenosis, indicating that this model corresponds to clinical cases that show rapid deterioration. Hence, the results of this study suggest that PDT is effective for clinical cases of airway stenosis that rapidly develops over a period of several days.

PDT was effective on most of the animals in the present study, but the effect of PDT was not sufficient in some animals, which showed temporary improvement in stenosis but died of restenosis. Histologic examination, however, revealed that there were traces of PDT effects, such as vacuole formation, even in these restenotic cases. These results suggest that the inhibitory effect of PDT on stenosis progression was not sufficient in the rabbits that died in the early phase after PDT, although PDT induced partial remission of the stenotic lesion and temporally delayed the stenosis progression. One possible reason for the insufficient effect of PDT in some cases is the laser irradiation method. We performed laser irradiation by monitoring under a bronchoscope; however, it was still difficult to handle the fiber tip in the extremely narrowed cavity of the trachea, resulting in insufficient light energy for the lesion. In this study, the cylindrical diffuser tip allowed us to irradiate the tracheal surface circumferentially,33 but the light may not have been homogenously delivered to the stenotic lesion since the lesion surface was highly irregular owing to the focal inconsistency of granulation tissue growth. The laser irradiation method should be further improved so that PDT can be established as a therapeutic modality for tracheal stenosis.

Some cases in the PDT group showed redness and edema of the nonscraped tracheal mucosa that was located in a region caudal to the trachea incision line, but these pathologic responses had almost disappeared 10 days after PDT. Murrer et al35 reported that photoirradiation of the normal trachea in porfimer sodium-treated pigs induced acute inflammation, edema, and vascular damage but that the acute-phase reactions recovered within 14 days. In this study, redness and edema were remitted in the early phase, and prolonged inflammation and hyperplasia of granulation tissue on the nonscraping area were not observed.

Recently, the fatality of immature infants has been improved, resulting in an increase number of children that need prolonged intubation in a neonatal ICUs. The number of cases of airway stenosis has therefore been increasing. Although surgical ablation is the standard treatment for airway stenosis, it is highly invasive, involving a high risk for low-weight and immature infants. Accordingly, conservative treatment methods are preferred for affected infants who are at high risk. Balloon dilatation, laser ablation, and stent implantation via a transtracheal approach using a bronchoscope have been the therapeutic methods with relatively low risk. Balloon dilatation and laser ablation have been reported to cause injuries to the respiratory tract, such as perforation, fatal hemorrhage, and tracheoesophageal fistulation.11 Although stent implantation appears to be a promising approach, there is a risk of displacement and/or mechanical fatigue of stents, resulting in restenosis due to granulation tissue proliferation.12 Accordingly, outcomes from these low invasive therapies are not always satisfactory: the percentage of patients who showed a complete remission with an uncomplicated course is not so high.8 PDT is much less invasive than the above therapeutic modalities. Actually, complications such as perforation of the respiratory tract and tracheoesophageal fistula were not seen in this study. Therefore, PDT might be a safe approach for patients for whom a surgical procedure involves a high risk. Moreover, we believe that PDT can also be used for the prevention of airway stenosis and plan to study the effectiveness of PDT in chronic airway stenosis models.

Conclusions

We examined whether PDT using porfimer sodium was effective for airway stenosis in rabbit models. This therapeutic approach resulted in reduction of granulation tissue in the stenotic lesion and prolongation of survival time of the treated animals. These results suggest that PDT has potential as a new method for ameliorating airway stenosis originating from granulation tissue.

Footnotes

Abbreviation: PDT = photodynamic therapy

This study was performed at the Department of Medical Engineering, National Defense Medical College.

This study was supported in part by Kawano Masanori Memorial Foundation for Promotion of Pediatrics, and The Japanese Foundation for Research and Promotion of Endoscopy.

The authors have no conflicts of interest to disclose.

Received for publication January 5, 2007. Accepted for publication August 2, 2007.

References

  1. Mathisen, DJ (1998) Surgery of the trachea. Curr Probl Surg 35,453-542[Medline]
  2. McDonald, IH, Stocks, JG Prolonged nasotracheal intubation: a review of its development in a paediatric hospital. Br J Anaesth 1965;37,161-173[Abstract/Free Full Text]
  3. Cotton, RT The problem of pediatric laryngotracheal stenosis: a clinical and experimental study on the efficacy of autogenous cartilaginous grafts placed between the vertically divided halves of the posterior lamina of the cricoid cartilage. Laryngoscope 1991;101,1-34[ISI][Medline]
  4. Nicklaus, PJ, Crysdale, WS, Conley, S, et al Evaluation of neonatal subglottic stenosis: a 3-year prospective study. Laryngoscope 1990;100,1185-1190[ISI][Medline]
  5. Ratner, I, Whitfield, J Acquired subglottic stenosis in the very-low-birth-weight infant. Am J Dis Child 1983;137,40-43[Abstract]
  6. Sherman, JM, Lowitt, S, Stephenson, C, et al Factors influencing acquired subglottic stenosis in infants. J Pediatr 1986;109,322-327[CrossRef][ISI][Medline]
  7. Preciado, D, Cotton, RT, Rutter, MJ Single-stage tracheal resection for severe tracheal stenosis in older children. Int J Pediatr Otorhinolaryngol 2004;68,1-6[CrossRef][ISI][Medline]
  8. Grillo, HC, Donahue, DM, Mathisen, DJ, et al Postintubation tracheal stenosis: treatment and results. J Thorac Cardiovasc Surg 1995;109,486-492[Abstract/Free Full Text]
  9. Wright, CD, Graham, BB, Grillo, HC, et al Pediatric tracheal surgery. Ann Thorac Surg 2002;74,308-313[Abstract/Free Full Text]
  10. Weber, TR, Connors, RH, Tracy, TF, Jr Acquired tracheal stenosis in infants and children. J Thorac Cardiovasc Surg 1991;102,29-34[Abstract]
  11. Personne, C, Colchen, A, Leroy, M, et al Indications and technique for endoscopic laser resections in bronchology: a critical analysis based upon 2,284 resections. J Thorac Cardiovasc Surg 1986;91,710-715[Abstract]
  12. Burningham, AR, Wax, MK, Andersen, PE, et al Metallic tracheal stents: complications associated with long-term use in the upper airway. Ann Otol Rhinol Laryngol 2002;111,285-290[ISI][Medline]
  13. Macdonald, IJ, Dougherty, TJ Basic principles of photodynamic therapy. J Porphyrins Phthalocyanines 2001;5,105-129[CrossRef]
  14. Oleinick, NL, Evans, HH The photobiology of photodynamic therapy: cellular targets and mechanisms. Radiat Res 1998;150,S146-156[ISI][Medline]
  15. Henderson, BW, Dougherty, TJ How does photodynamic therapy work? Photochem Photobiol 1992;55,145-157[ISI][Medline]
  16. Chang, CJ, Sun, CH, Liaw, LH, et al In vitro and in vivo photosensitizing capabilities of 5-ALA versus Photofrin in vascular endothelial cells. Lasers Surg Med 1999;24,178-186[CrossRef][ISI][Medline]
  17. Peng, Q, Berg, K, Moan, J, et al 5-Aminolevulinic acid-based photodynamic therapy: principles and experimental research. Photochem Photobiol 1997;65,235-251[ISI][Medline]
  18. Obana, A, Gohto, Y, Kaneda, K, et al Selective occlusion of choroidal neovascularization by photodynamic therapy with a water-soluble photosensitizer, ATX-S10. Lasers Surg Med 1999;24,209-222[CrossRef][ISI][Medline]
  19. Kramer, M, Miller, JW, Michaud, N, et al Liposomal benzoporphyrin derivative verteporfin photodynamic therapy: selective treatment of choroidal neovascularization in monkeys. Ophthalmology 1996;103,427-438[ISI][Medline]
  20. Tang, G, Hyman, S, Schneider, JH, Jr, et al Application of photodynamic therapy to the treatment of atherosclerotic plaques. Neurosurgery 1993;32,438-443[ISI][Medline]
  21. Hsiang, YN, Crespo, MT, Machan, LS, et al Photodynamic therapy for atherosclerotic stenoses in Yucatan miniswine. Can J Surg 1994;37,148-152[ISI][Medline]
  22. Nakagishi, Y, Morimoto, Y, Fujita, M, et al Accumulation of Photofrin in lesions of airway stenosis rabbit models. Photochem Photobiol 2007;83,1220-1225[CrossRef][ISI][Medline]
  23. Kato, H, Okunaka, T, Shimatani, H Photodynamic therapy for early stage bronchogenic carcinoma. J Clin Laser Med Surg 1996;14,235-238[Medline]
  24. Moan, J, Berg, K Photochemotherapy of cancer: experimental research. Photochem Photobiol 1992;55,931-948[ISI][Medline]
  25. Dougherty, TJ, Gomer, CJ, Henderson, BW, et al Photodynamic therapy. J Natl Cancer Inst 1998;90,889-905[Abstract/Free Full Text]
  26. Nakagishi, Y, Morimoto, Y, Fujita, M, et al Rabbit model of airway stenosis induced by scraping of the tracheal mucosa. Laryngoscope 2005;115,1087-1092[CrossRef][ISI][Medline]
  27. National Institutes of Health, Office of Science and Health Reports.. Guide for the care and use of laboratory animals, revised 1996. National Institutes of Health. Bethesda, MD: Department of Health, Education, and Welfare publication NIH 85–23
  28. White, GL, Holmes, DD A comparison of ketamine and the combination ketamine-xylazine for effective surgical anesthesia in the rabbit. Lab Anim Sci 1976;26,804-806[ISI][Medline]
  29. Ferrario, A, Fisher, AM, Rucker, N, et al Celecoxib and NS-398 enhance photodynamic therapy by increasing in vitro apoptosis and decreasing in vivo inflammatory and angiogenic factors. Cancer Res 2005;65,9473-9478[Abstract/Free Full Text]
  30. Lilge, L, Portnoy, M, Wilson, BC Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue. Br J Cancer 2000;83,1110-1117[CrossRef][ISI][Medline]
  31. Amemiya, T, Nakajima, H, Katoh, T, et al Photodynamic therapy of atherosclerosis using YAG-OPO laser and porfimer sodium, and comparison with using argon-dye laser. Jpn Circ J 1999;63,288-295[CrossRef][Medline]
  32. Hsiang, YN, Todd, ME, Bower, RD Determining light dose for photodynamic therapy of atherosclerotic lesions in the Yucatan miniswine. J Endovasc Surg 1995;2,365-371[CrossRef][ISI][Medline]
  33. Lilge, L, Vesselov, L, Whittington, W Thin cylindrical diffusers in multimode Ge-doped silica fibers. Lasers Surg Med 2005;36,245-251[CrossRef][ISI][Medline]
  34. Fisher, AM, Murphree, AL, Gomer, CJ Clinical and preclinical photodynamic therapy. Lasers Surg Med 1995;17,2-31[ISI][Medline]
  35. Murrer, LH, Hebeda, KM, Marijnissen, JP, et al Short- and long-term normal tissue damage with photodynamic therapy in pig trachea: a fluence-response pilot study comparing Photofrin and mTHPC. Br J Cancer 1999;80,744-755[CrossRef][ISI][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
chest.07-1410v1
133/1/123    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nakagishi, Y.
Right arrow Articles by Kikuchi, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakagishi, Y.
Right arrow Articles by Kikuchi, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS