0
Selected Reports |

Successful Treatment of Juvenile Laryngeal Papillomatosis-Related Multicystic Lung Disease With Cidofovir* Case Report and Review of the Literature FREE TO VIEW

David R. Dancey, MD; Dean W. Chamberlain, MD; Mel Krajden, MD; Joel Palefsky, MD; P.W. Alberti, MD; Gregory P. Downey, MD, FCCP
Author and Funding Information

Affiliations: *From the Division of Respirology (Drs. Dancey and Downey) and the Division of Medical Microbiology (Dr. Krajden), Department of Medicine, the Department of Laboratory Medicine and Pathobiology (Dr. Chamberlain), and the Division of Otolaryngology (Dr. Alberti), Department of Surgery, University of Toronto, Ontario, Canada; and the Department of Laboratory Medicine (Dr. Palefsky), University of California, San Francisco, CA. ,  Current address: Provincial Lab, British Columbia Centre for Disease Control, Vancouver, British Colombia, Canada.

Correspondence to: Gregory P. Downey, MD, FCCP, EN 10–212, The Toronto General Hospital, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4; e-mail: gregory.downey@utoronto.ca



Chest. 2000;118(4):1210-1214. doi:10.1378/chest.118.4.1210
Text Size: A A A
Published online

Cidofovir, a nucleoside analog antiviral agent, has been used with moderate success in the treatment of juvenile laryngeal papillomatosis (JLP) by direct intralesional injection. We report the first case where IV cidofovir was used successfully to treat a rare but lethal multicystic lung disease complicating JLP. A 35-year-old woman with a history of JLP requiring multiple laser ablations of laryngeal papillomata each year presented with hemoptysis and was found on CT scan to have bilateral, multiple pulmonary nodules and cysts. The results of BAL fluid analysis demonstrated no evidence of malignancy, and cultures were negative for fungi and mycobacteria. Molecular DNA typing of a biopsy specimen obtained from a laryngeal papilloma confirmed infection with human papilloma virus type 11. She received 12 months of treatment with IV cidofovir followed by 9 months of combined treatmentwith IV cidofovir and subcutaneous interferon-α-2A. This therapeutic regime resulted in a markedly decreased requirement for surgical removal of laryngeal papillomata, and CT scanning documented the regression of the lesions in the lung parenchyma that persisted after the discontinuation of therapy. The results of this case demonstrate that cidofovir may be used successfully to treat JLP-related lung disease and suggest that further studies are warranted.

Figures in this Article

Laryngeal papillomatosis, a condition characterized by relapsing, benign, epithelial neoplastic polyps in the larynx, is caused by infection with the human papillomavirus (HPV).1 In the United States, the juvenile-onset form of the disease (juvenile laryngeal papillomatosis [JLP]) is diagnosed in 1,500 children each year.2JLP usually resolves at puberty but can persist into adulthood.3 Although the condition is usually limited to the larynx, it involves the tracheobronchial tree in 2 to 5% of cases and the lung parenchyma in 1% of cases.1

Since the first report in 1932 of lung parenchymal disease complicating JLP, there have been a total of 16 cases reported in the English language literature.1,418 In six of the cases, the patients had died at the time of the report. Five additional cases are not included because of the presence of lung cancer, which made conclusions about JLP-related parenchymal disease difficult to reach.10,1921 Treatment of the lung complications has varied considerably but has generally been unsuccessful. Despite the knowledge that the disease is a result of an infection with HPV, until recently antiviral drugs have not been used.

Nucleoside analog antiviral medications, such as acyclovir and ganciclovir, are standard treatments for infections with herpes simplex, varicella zoster, and cytomegalovirus.2224 A newer generation of nucleoside analog, cidofovir (Pharmacia & Upjohn; Mississauga, ON, Canada), has been reported to be successful in treating HPV in patients with esophageal or anal lesions.2526 In addition, Snoek et al27 have reported success using intralesional injections of cidofovir to treat 17 patients with severe, local JLP. We report a case of lung parenchymal disease complicating JLP that was successfully treated with IV cidofovir.

A 35-year-old woman with a history of laryngeal papillomatosis since infancy was evaluated for hemoptysis and progressive dyspnea on exertion. Three weeks prior to referral, she had an episode of retrosternal chest pain and shaking chills that lasted for 8 h. One week later, she developed daily episodes of hemoptysis and progressively worsening dyspnea.

Since infancy, she had been treated for laryngeal papillomatosis with multiple laryngoscopic resections and, more recently, with laser ablation. At the time of referral, she had had a total of 96 resections and laser ablations, with 4 laser treatments in the preceding year.

A physical examination revealed a woman with a hoarse voice and audible wheeze who was not in respiratory distress. Her vital signs were normal, and she had no evidence of lymphadenopathy, clubbing, peripheral cyanosis, hepatosplenomegaly, rash, or active arthritis. A chest examination was remarkable for faint wheezes on both inspiration and expiration, which were loudest at the neck.

Laryngoscopy demonstrated multiple laryngeal papillomata, and laser ablation was performed with the resolution of her dyspnea. A high-resolution CT scan of the thorax (Fig 1 ) demonstrated multiple, bilateral nodules and thin-walled cysts, with the largest cyst measuring 2 cm in maximum dimension. Fiberoptic bronchoscopy was performed under a local anesthetic. Neither mucosal abnormalities nor the source of hemoptysis was identified.

Four months later, the patient required another laser treatment for the recurrence of her laryngeal disease. Rigid bronchoscopy was performed at the time, with excellent visualization of the trachea, right and left mainstem bronchi, and bronchus intermedius. Although several laryngeal papillomas were obvious, no endobronchial lesions were seen. HPV type 11 was identified in a sample of the resected papilloma. A lung biopsy was recommended, but the patient declined. A presumptive diagnosis of HPV-related multicystic lung disease was made. She was followed with serial high-resolution CT scans of her thorax. Because of increasing pulmonary parenchymal nodules and cysts, antiviral treatment was considered.

Treatment with cidofovir (Vistide; Gilead Sciences; Foster City, CA) was begun at a dose of 5 mg/kg administered every 2 weeks in conjunction with probenecid in order to diminish nephrotoxicity. The patient’s CBC count and differential count, serum creatinine levels, and urinalysis results were monitored weekly. Two months after treatment was begun, she had an anaphylactic reaction to probenecid, which was discontinued. She continued to receive cidofovir, receiving aggressive hydration (6 L IV saline solution before treatment and 3 L oral hydration after treatment) to prevent nephrotoxicity. Following 12 months of treatment, a CT scan of the thorax demonstrated regression of the pulmonary parenchymal nodules and cysts (Fig 1). In addition, her need for laser polypectomy decreased considerably; only two laser treatments were required in the year during treatment compared with five and four in each of the two preceding years.

Following 12 months of treatment with cidofovir, interferon-α-2A was added as an immune-enhancing agent in anticipation of the cessation of cidofovir therapy. The initial dose was 3 million units subcutaneously daily for 1 month, which then was reduced to 3 million units three times weekly. Four months later, partial alopecia and leukopenia developed, requiring a dose reduction of both agents. Interferon-α-2A therapy was stopped after a total of 9 months of treatment. Cidofovir was continued at a dose of 4 mg/kg every 2 weeks for an additional 12 weeks and then was stopped after the patient had received a total of 51 doses.

At present, 18 months after the cessation of all therapy, she continues to do well and has required laser polypectomy only once. Pulmonary function testing shows normal lung volumes, diffusion capacity, and airflow, including a maximum inspiratory flow at 50% of vital capacity of 3.66 L (232% of predicted). The most recent CT scan of the thorax demonstrated a stabilization of her parenchymal disease after a total of 24 months of therapy.

Although rare, extralaryngeal disease in patients with JLP does occur and portends a poor prognosis. Clinical clues may include fever, hemoptysis, sputum production, or progressive dyspnea despite control of the laryngeal disease.1,418 Only one case of lower respiratory tract involvement has been reported in the absence of laryngeal disease.28 Bronchoscopy may demonstrate lesions throughout the tracheobronchial tree, suggesting possible parenchymal lung involvement.20 Chest radiographs have shown persistent postobstructive atelectasis,7,10 recurrent airspace consolidation,6,1011,18 recurrent pneumothoraces,1 and nodules with and without cavitation.6,8,1214,17 Chest CT scans have demonstrated multiple nodules, with or without cavitation, as well as thin-walled cysts.

Despite moderate success using interferon-α-2A to treat JLP that is limited to the larynx,29 attempts to treat lung involvement have been largely empiric and unsuccessful. In all cases, the pathology of the biopsy or autopsy specimens has been identical to that of the laryngeal lesions. Antibiotics, surgery, autogenous vaccine, transfer factor, and chemotherapy, including cyclophosphamide, methotrexate, bleomycin, and interferon, have been tried without success.1,418

It has been only in the last 2 to 3 years that antiviral drugs have been used to treat this disease. In the early 1980s, molecular diagnostic technology enabled the identification of HPV as the etiologic agent of JLP.30HPV type 6 appears to be most commonly associated with extralaryngeal involvement.31 Despite this knowledge, the first report of the use of antiviral agents to treat JLP was published in 1998.27

Cidofovir (also known as HPMPC, GS-0504, and 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate) is a cytosine nucleoside analog that has been shown both in vitro and in vivo to be active against the Herpesvirus group.3233 The main indication for its use has been in suppressing cytomegalovirus retinitis complicating AIDS.3435 The dose-limiting toxicity of cidofovir is renal failure from acute tubular necrosis. This condition was observed in AIDS patients at doses of 3 and 5 mg/kg given once weekly for 2 weeks then biweekly but was prevented using probenecid and hydration prior to each dose. Reversible neutropenia was the next most common adverse effect seen.3435

Two case reports on the use of cidofovir against HPV in humans were published in 1995. In one case, local injections of the drug into a squamous papilloma of the hypopharynx-esophagus successfully eradicated the lesion.26 In the second case, three patients with AIDS and relapsing anal warts received cidofovir topically with complete resolution of the warts.25 No significant adverse effects were noted. Most recently, intralesional injections of cidofovir were used to successfully treat 17 patients with severe, localized JLP.27

During the 24 months of treatment with cidofovir, our patient demonstrated a markedly diminished requirement for laser polypectomies, and serial CT scans demonstrated the regression and then the stabilization of the parenchymal nodules and cysts (Fig 1). The pulmonary parenchymal lesions have not progressed despite the discontinuation of all antiviral therapy, and the patient has not required a laser polypectomy for the 18 months since treatment was stopped, suggesting that the effects of cidofovir have persisted long after the discontinuation of the medication.

To our knowledge, this is the first report of the use of systemic cidofovir for treating parenchymal lung disease complicating JLP. Because it is such a rare complication of JLP, it is unlikely there will be an opportunity for a randomized, controlled trial to properly evaluate the efficacy of cidofovir in treating HPV-related multicystic lung disease. However, given the success in eradicating other forms of HPV infection with intralesional injections, it is reasonable to assume that lung lesions would respond similarly. In principal, bronchoscopic or CT-guided injections of cidofovir could be used to treat symptomatic parenchymal lesions, avoiding the systemic toxicities of the drug. Nevertheless, larger, randomized studies are needed to confirm the efficacy of cidofovir therapy in patients with JLP. Aggressive treatment of the disease at its onset may successfully prevent its complications.

Abbreviations: HPV = human papilloma virus; JLP = juvenile laryngeal papillomatosis

Figure Jump LinkFigure 1. High-resolution CT scan images of the thorax demonstrating multiple nodular and cystic lesions (top, A) prior to treatment with cidofovir and (bottom, B) following 12 months of treatment. Note the regression in the nodular and cystic lesions.Grahic Jump Location
Anderson, KC, Roy, TM, Fields, CL, et al (1993) Juvenile laryngeal papillomatosis: a new complication.South Med J86,447-449. [CrossRef] [PubMed]
 
Mounts, P, Shah, KV Respiratory papillomatosis: etiological relation to genital tract papillomaviruses. Melnick, JL eds.Progress in medical virology (vol 29)1984,90-114 Karger AG. New York, NY:
 
Gaylis, B, Hayden, RE Recurrent respiratory papillomatosis: progression to invasion and malignancy.Am J Otolaryngol1991;12,104-112. [CrossRef] [PubMed]
 
Hitz, HB, Oesterlin, E A case of multiple papillomata of the larynx with aerial metastases to lungs.Am J Pathol1932;8,333-338. [PubMed]
 
Buffmire, DK, Clagett, OT, McDonald, JR Papillomas of the larynx, trachea and bronchi.Mayo Clin Proc1950;25,595-600
 
Kirchner, JA Papilloma of the larynx with extensive lung involvement.Laryngoscope1951;61,1022-1029. [CrossRef] [PubMed]
 
Castleman, B, Towne, VW Case records of the Massachusetts General Hospital.N Engl J Med1957;257,465-471. [CrossRef] [PubMed]
 
Moore, RL, Lattes, R Papillomatosis of the larynx and bronchi: case report with 34 year follow-up.Cancer1959;12,117-126. [CrossRef] [PubMed]
 
Singer, DB, Greenberg, SD, Harrison, GM Papillomatosis of the lung.Am Rev Respir Dis1966;94,777-783. [PubMed]
 
Al-Saleem, T, Peale, AR, Norris, CM Multiple papillomatosis of the lower respiratory tract.Cancer1968;22,1173-1184. [CrossRef] [PubMed]
 
Rosenbaum, HD, Alavi, SM, Bryant, LR Pulmonary parenchymal spread of juvenile laryngeal papillomatosis.Radiology1968;90,654-668. [PubMed]
 
Justus J, Baerthold W, Preibisch-Effenberger R. Juvenile larynxpapillomatose mit ausbreitung uber das tracheobronchialsystem und maligne entartung ohne strahlentherapie. HNO (Berlin) 1970; 18:349–354.
 
Smith, L, Gooding, CA Pulmonary involvement in laryngeal papillomatosis.Pediatr Radiol1974;2,161-166. [CrossRef] [PubMed]
 
Glazer, G, Webb, WR Laryngeal papillomatosis with pulmonary spread in a 69 year-old man.AJR Am J Roentgenol1979;132,820-822. [PubMed]
 
Iijima, T, Hatakeyama, N, Yanagimachi, Y, et al A case of pulmonary papillomatosis [in Japanese].Rinsho Hoshasen1981;26,965-970. [PubMed]
 
Borkowsky, W, Martin, D, Lawrence, HS Juvenile laryngeal papillomatosis with pulmonary spread: regression following transfer factor therapy.Am J Dis Child1984;138,667-669. [PubMed]
 
Kawanami, T, Bowen, A Juvenile laryngeal papillomatosis with pulmonary parenchymal spread: case report and review of the literature.Pediatr Radiol1985;15,102-104. [CrossRef] [PubMed]
 
Kerley, SW, Buchon-Zalles, C, Moran, J, et al Chronic cavitary respiratory papillomatosis.Arch Pathol Lab Med1989;113,1166-1169. [PubMed]
 
Kaufman, G, Klopstock, R Papillomatosis of the larynx and trachea.Am Rev Respir Dis1963;88,839-846. [PubMed]
 
Brach, BB, Klein, RC, Mathews, AJ, et al Papillomatosis of the lower respiratory tract: upper airway obstruction and carcinoma.Arch Otolaryngol1978;104,413-416. [CrossRef] [PubMed]
 
Runckel, D, Kessler, S Bronchogenic squamous carcinoma in nonirradiated juvenile laryngotracheal papillomatosis.Am J Surg Pathol1980;4,293-296. [CrossRef] [PubMed]
 
Greenberg, SB Human interferon in viral diseases.Infect Dis Clin North Am1987;1,383-423. [PubMed]
 
Patel, P, Gemmell, R, Carruth, JA Inosine pranobex in recurrent laryngeal papillomatosis.J Laryngol Otol1987;101,1306-1307. [CrossRef] [PubMed]
 
Strander, HA Interferon in the treatment of human papilloma virus.Med Clin North Am1986;May(suppl),19-23
 
Snoek, R, van Ranst, M, Andrei, G Treatment of anogenital papillomavirus infections with an acyclic nucleoside phosphonate analogue.N Engl J Med1995;333,943-944
 
van Cutsem, E, Snoek, R, van Ranst, M, et al Successful treatment of squamous papilloma of the hypopharynx-esophagus by local injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine.J Med Virol1995;45,230-235. [CrossRef] [PubMed]
 
Snoek, R, Wellens, W, Desloovere, C, et al Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir [(S)-1-(3-hydroxy-2- phosphonylmethoxypropyl)cytosine].J Med Virol1998;54,219-225. [CrossRef] [PubMed]
 
Elliott, GB, Belkin, A, Donald, WAJ Cystic bronchial papillomatosis.Clin Radiol1962;13,62-67. [CrossRef]
 
Deunas, L, Alcantud, V, Alvarez, F, et al Use of interferon-alpha in laryngeal papillomatosis: eight years of the Cuban national programme.J Laryngol Otol1997;111,134-140. [PubMed]
 
Gissman, L, Diehl, V, Schultz-Coulon, HJ, et al Molecular cloning and characterization of human papilloma virus DNA derived from a laryngeal papilloma.J Virol1982;44,393-402. [PubMed]
 
Mounts, P, Kashima, H Association of human papillomavirus subtype and clinical course in respiratory papillomatosis.Laryngoscope1984;94,28-33. [PubMed]
 
Biron, K, Stanet, S, Sorrell, J, et al Metabolic activation of the nucleoside analog 9-[2- hydroxy-1-(hydroxymethyl)-ethoxy]-methylguanine in human diploid fibroblasts infected with human cytomegalovirus.Proc Natl Acad Sci USA1985;82,2473-2477. [CrossRef] [PubMed]
 
Ho, H, Woods, K, Bronson, JJ, et al Intracellular metabolism of the antiherpes agent (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine.Mol Pharmacol1991;41,197-202
 
Lalezari, JP, Stagg, RJ, Baruch, D, et al Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS.Ann Intern Med1997;6,257-263
 
AIDS Research Group/AIDS Clinical Trials Group. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HMPC peripheral cytomegalovirus retinitis trial; a randomized, controlled trial—Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group.Ann Intern Med1997;126,264-274. [PubMed]
 

Figures

Figure Jump LinkFigure 1. High-resolution CT scan images of the thorax demonstrating multiple nodular and cystic lesions (top, A) prior to treatment with cidofovir and (bottom, B) following 12 months of treatment. Note the regression in the nodular and cystic lesions.Grahic Jump Location

Tables

References

Anderson, KC, Roy, TM, Fields, CL, et al (1993) Juvenile laryngeal papillomatosis: a new complication.South Med J86,447-449. [CrossRef] [PubMed]
 
Mounts, P, Shah, KV Respiratory papillomatosis: etiological relation to genital tract papillomaviruses. Melnick, JL eds.Progress in medical virology (vol 29)1984,90-114 Karger AG. New York, NY:
 
Gaylis, B, Hayden, RE Recurrent respiratory papillomatosis: progression to invasion and malignancy.Am J Otolaryngol1991;12,104-112. [CrossRef] [PubMed]
 
Hitz, HB, Oesterlin, E A case of multiple papillomata of the larynx with aerial metastases to lungs.Am J Pathol1932;8,333-338. [PubMed]
 
Buffmire, DK, Clagett, OT, McDonald, JR Papillomas of the larynx, trachea and bronchi.Mayo Clin Proc1950;25,595-600
 
Kirchner, JA Papilloma of the larynx with extensive lung involvement.Laryngoscope1951;61,1022-1029. [CrossRef] [PubMed]
 
Castleman, B, Towne, VW Case records of the Massachusetts General Hospital.N Engl J Med1957;257,465-471. [CrossRef] [PubMed]
 
Moore, RL, Lattes, R Papillomatosis of the larynx and bronchi: case report with 34 year follow-up.Cancer1959;12,117-126. [CrossRef] [PubMed]
 
Singer, DB, Greenberg, SD, Harrison, GM Papillomatosis of the lung.Am Rev Respir Dis1966;94,777-783. [PubMed]
 
Al-Saleem, T, Peale, AR, Norris, CM Multiple papillomatosis of the lower respiratory tract.Cancer1968;22,1173-1184. [CrossRef] [PubMed]
 
Rosenbaum, HD, Alavi, SM, Bryant, LR Pulmonary parenchymal spread of juvenile laryngeal papillomatosis.Radiology1968;90,654-668. [PubMed]
 
Justus J, Baerthold W, Preibisch-Effenberger R. Juvenile larynxpapillomatose mit ausbreitung uber das tracheobronchialsystem und maligne entartung ohne strahlentherapie. HNO (Berlin) 1970; 18:349–354.
 
Smith, L, Gooding, CA Pulmonary involvement in laryngeal papillomatosis.Pediatr Radiol1974;2,161-166. [CrossRef] [PubMed]
 
Glazer, G, Webb, WR Laryngeal papillomatosis with pulmonary spread in a 69 year-old man.AJR Am J Roentgenol1979;132,820-822. [PubMed]
 
Iijima, T, Hatakeyama, N, Yanagimachi, Y, et al A case of pulmonary papillomatosis [in Japanese].Rinsho Hoshasen1981;26,965-970. [PubMed]
 
Borkowsky, W, Martin, D, Lawrence, HS Juvenile laryngeal papillomatosis with pulmonary spread: regression following transfer factor therapy.Am J Dis Child1984;138,667-669. [PubMed]
 
Kawanami, T, Bowen, A Juvenile laryngeal papillomatosis with pulmonary parenchymal spread: case report and review of the literature.Pediatr Radiol1985;15,102-104. [CrossRef] [PubMed]
 
Kerley, SW, Buchon-Zalles, C, Moran, J, et al Chronic cavitary respiratory papillomatosis.Arch Pathol Lab Med1989;113,1166-1169. [PubMed]
 
Kaufman, G, Klopstock, R Papillomatosis of the larynx and trachea.Am Rev Respir Dis1963;88,839-846. [PubMed]
 
Brach, BB, Klein, RC, Mathews, AJ, et al Papillomatosis of the lower respiratory tract: upper airway obstruction and carcinoma.Arch Otolaryngol1978;104,413-416. [CrossRef] [PubMed]
 
Runckel, D, Kessler, S Bronchogenic squamous carcinoma in nonirradiated juvenile laryngotracheal papillomatosis.Am J Surg Pathol1980;4,293-296. [CrossRef] [PubMed]
 
Greenberg, SB Human interferon in viral diseases.Infect Dis Clin North Am1987;1,383-423. [PubMed]
 
Patel, P, Gemmell, R, Carruth, JA Inosine pranobex in recurrent laryngeal papillomatosis.J Laryngol Otol1987;101,1306-1307. [CrossRef] [PubMed]
 
Strander, HA Interferon in the treatment of human papilloma virus.Med Clin North Am1986;May(suppl),19-23
 
Snoek, R, van Ranst, M, Andrei, G Treatment of anogenital papillomavirus infections with an acyclic nucleoside phosphonate analogue.N Engl J Med1995;333,943-944
 
van Cutsem, E, Snoek, R, van Ranst, M, et al Successful treatment of squamous papilloma of the hypopharynx-esophagus by local injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine.J Med Virol1995;45,230-235. [CrossRef] [PubMed]
 
Snoek, R, Wellens, W, Desloovere, C, et al Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir [(S)-1-(3-hydroxy-2- phosphonylmethoxypropyl)cytosine].J Med Virol1998;54,219-225. [CrossRef] [PubMed]
 
Elliott, GB, Belkin, A, Donald, WAJ Cystic bronchial papillomatosis.Clin Radiol1962;13,62-67. [CrossRef]
 
Deunas, L, Alcantud, V, Alvarez, F, et al Use of interferon-alpha in laryngeal papillomatosis: eight years of the Cuban national programme.J Laryngol Otol1997;111,134-140. [PubMed]
 
Gissman, L, Diehl, V, Schultz-Coulon, HJ, et al Molecular cloning and characterization of human papilloma virus DNA derived from a laryngeal papilloma.J Virol1982;44,393-402. [PubMed]
 
Mounts, P, Kashima, H Association of human papillomavirus subtype and clinical course in respiratory papillomatosis.Laryngoscope1984;94,28-33. [PubMed]
 
Biron, K, Stanet, S, Sorrell, J, et al Metabolic activation of the nucleoside analog 9-[2- hydroxy-1-(hydroxymethyl)-ethoxy]-methylguanine in human diploid fibroblasts infected with human cytomegalovirus.Proc Natl Acad Sci USA1985;82,2473-2477. [CrossRef] [PubMed]
 
Ho, H, Woods, K, Bronson, JJ, et al Intracellular metabolism of the antiherpes agent (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine.Mol Pharmacol1991;41,197-202
 
Lalezari, JP, Stagg, RJ, Baruch, D, et al Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS.Ann Intern Med1997;6,257-263
 
AIDS Research Group/AIDS Clinical Trials Group. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HMPC peripheral cytomegalovirus retinitis trial; a randomized, controlled trial—Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group.Ann Intern Med1997;126,264-274. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
CHEST Collections
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543