RRP Medical Reference Service
An RRP Foundation Publication
Dave Wunrow and Bill Stern
Volume 4 Number 2
The RRP Medical Reference Service is intended to be of potential interest to RRP patients/families seeking treatment, practitioners providing care, micro biological researchers as well as others interested in developing a comprehensive understanding of recurrent respiratory papillomatosis.
This issue focuses on a selection of references with abstracts from recent (all but one are from 1995 and later) RRP related publications.These listings are sorted in approximate reverse chronological order as indicated by the "Unique Identifier" numbers. Each listing is formatted as follows:
Journal or reference
Language (if it is not specified assume article is in English)
Primary affiliation (when specified)
If copies of complete articles are desired, we suggest that you request a reprint from one of the authors. If you need assistance in this regard or if you have any other questions or comments please feel free to contact:
P.O. Box 6643
Lawrenceville NJ 08648-0643
(609) 530-1443 or (609)452-6545
E-mail: email@example.com or firstname.lastname@example.org
210 Columbus Drive
Marshfield WI 54449
RRPF Selected Articles and Abstracts
Am J Otol 1997 Jul-Aug; 18 (4) :283-285
Treatment of Recurrent Respiratory Papillomatosis with Indole-3-Carbinol.
Coll D, Rosen C, Auborn K, Potsic W, Bradlow HL
Department of Otolaryngology - Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.
Unique Identifier: 97386793
Recurrent respiratory papillomatosis (RRP) is a rare disease characterized by benign papillomatous growths of the aerodigestive mucosa. RRP is the most common benign laryngeal tumor of childhood, but it affects all age groups, with approximately 2,350 new pediatric cases and 3,600 new adult cases diagnosed in a 1-year period in the United States. The papillomas may develop anywhere in the aero-digestive tract with the true vocal folds being the most commonly affected site. Hoarseness is the most frequent presenting symptom. Other symptoms may include stridor, dyspnea, failure to thrive, chronic cough, and recurrent pneumonia, symptoms often mistakenly attributed to asthma, croup, chronic tonsillitis, or allergies. The course of RRP varies considerably, and some patients may experience spontaneous remission, whereas others suffer from recurrent papillomatous growth. Malignant transformation, although uncommon, is well documented in RRP patients. The papillomas may produce respiratory obstruction and create a life threatening situation, especially in children. Frequent surgical removal is usually required to maintain an adequate airway, and tracheotomy is often necessaru in children with aggressive RRP. The human papilloma virus (HPV), types 6 and 11, has long been suspected of being the etiologic agent in RRP and has been identified in laryngeal papillomas. There is currently no effective treatment for HPV infection, and palliative surgical removal of papillomas has been the best means of controlling the symptoms of RRP. Alternative methods of treating RRP have had limited success. The considerable morbidity associated with this disease fuels the search for effective treatments of RRP. Indole-3-carbinol (I3C), a potent inducer of cytochrome P450 regulated metabolism of estrogen, has been shown to reduce the development of papillomatous tumors in HPV infected laryngeal tissue transplanted into immunocompromised nude mice. I3C is found in cruciferous vegetables, which includes cabbage, brussel sprouts, broccoli, and cauliflower. We present a case of a patient with aggressive recurrent laryngeal papillomatosis requiring multiple surgeries over a 6-month period. Her symptoms have not recurred, and subsequent examinations have found no papillomatous lesions since the initiation of dietary supplementation with I3C and continued I3C therapy over a period of 45 months.
Int J Cancer 1997 Mar 17;70(6):668-673
Cytogenetic analysis of inverted nasal papillomas and demonstration of genetic convergence during in vitro passaging.
Jin C, Jin Y, Wennerberg J, Akervall J, Dictor M, Mandahl N, Heim S, Mitelman F, Mertens F
Department of Clinical Genetics, University Hospital, Lund, Sweden. Charlotte.Jin@klingen.lu.se
Unique Identifier: 97250964
Three inverted nasal papillomas were cytogenetically investigated after short-term culture. Two of the cases were characterized by a single abnormal clone with t(1;8)(p36;q11) and trisomy 7, respectively, whereas the third papilloma showed extreme cytogenetic heterogeneity: of 852 analyzed cells, 329 belonged to 36 unrelated clones, 344 had non-clonal changes, and 179 had a normal chromosome constitution. The polyclonal papilloma was further analyzed during in vitro passage of 3 lines (L1-L3) cultured independently since initiation of the primary cultures and found to have 6, 16 and 6 unrelated clones at analysis of primary cultures. At passage 1, each line was further subdivided into 2 sub-lines (L1A and B, L2A and B, and L3A and B), which were cultured separately until the cells spontaneously stopped dividing. After 4 to 7 passages, each sub-line was dominated (83-98% of the cells) by a single clone. The cell populations that took over the cultures were the same within each set of sub-lines (A and B lines), demonstrating that clonal overgrowth in vitro is not random. The difference in clonal selection among the L1-L3 lines further shows that genetic convergence during in vitro growth in stable conditions is dependent not only on the clones' ability to adapt to the culture conditions, but also on the nature of the neighboring cells with which they collaborate and compete.
Acta Obstet Gynecol Scand 1997 Mar;76(3):271-276
Low-risk human papillomavirus types 6 and 11 associated with carcinomas of the genital and upper aero-digestive tract.
Turazza E, Lapena A, Sprovieri O, Torres CP, Gurucharri C, Maciel A, Lema B, Grinstein S, Kahn T
Virology Laboratory, Children's Hospital Ricardo Gutierrez, Buenos Aires, Argentina.
Unique Identifier: 97246999
BACKGROUND: Human papillomavirus (HPVs) types 6 and 11, are frequently found in non-malignant anogenital condylomas and laryngeal papillomas. However, in an ongoing epidemiological study in Argentina in which 163 anogenital and aero-respiratory cancer biopsies were analyzed, several cases infected with low-risk HPVs could be detected. METHODS: Tumor samples were analyzed by Southern blot hybridization, using HPVs 6, 11, 16, 18, 30, 31, 33 and 35 as probes, and polymerase chain reaction (PCR) with type-specific primers and probes. RESULTS: Four invasive carcinomas containing HPV 6 or 11 could be detected (2.4%) by Southern blot technique. HPV 6 DNA was found in a penile carcinoma, a groin carcinoma, and in a tonsillar carcinoma. One cervical carcinoma harbored HPV 11 DNA. Using HPVs 6, 11, 16, 18 and 33 anticontamination primers and probes in PCR, no additional high-risk HPV types could be detected in these four cancers. CONCLUSION: This report shows the presence of low-risk HPVs (HPV 6 and 11) associated to malignant tumors in a frequency higher than usually observed. The data raise questions about which are the circumstances which may favor low-risk HPV related oncogenesis.
Arch Otolaryngol Head Neck Surg 1997 Mar;123(3):297-300
p53 protein expression in benign lesions of the upper respiratory tract.
Ingle RR, Setzen G, Koltai PJ, Monte D, Pastore J, Jennings TA
Department of Pathology, Albany Medical College, NY, USA.
Unique Identifier: 97230805
OBJECTIVE: p53 is a tumor suppressor gene that is lost or mutated in most forms of human malignancy. There are, however, very few studies evaluating p53 expression in normal epithelium or benign lesions. DESIGN: We screened for p53 protein expression in a variety of benign epithelial lesions of upper respiratory tract using monoclonal antibody DO-1 on paraffin-embedded material. SUBJECTS: We studied a total of 109 cases: 16 cases of juvenile and 36 cases of adult laryngeal papillomatosis, 10 cases each of laryngeal nodules and laryngeal polyps, 17 cases of inverted papilloma, and 20 cases of nasal polyps. RESULTS: Nuclear immunoreactivity for p53 protein was demonstrated in 14 (88%) of 16 cases of juvenile laryngeal papillomatosis, 33 (92%) of 36 cases of adult laryngeal papillomatosis, 4 (40%) of 10 cases of laryngeal nodules, 8 (80%) of 10 cases of laryngeal polyps, 7 (41%) of 17 cases of inverted papilloma, and 2 (10%) of 20 cases of nasal polyps. These results pertained only to the basal epithelial layer in all cases of laryngeal nodules, laryngeal polyps, and nasal polyps. Intermediate layer cells were also positive for p53 in the majority of the cases of both juvenile (69%) and adult (75%) laryngeal papillomatosis and in a minority of the cases of inverted papilloma (18%). CONCLUSIONS: Overexpression of p53 protein is commonly demonstrable in benign epithelial lesions of the upper respiratory tract. This observation suggests that p53 protein accumulation may occur in the absence of mutation of the p53 gene and may correlate with epithelial proliferative activity.
J Laryngol Otol 1997 Feb;111(2):134-140
Use of interferon-alpha in laryngeal papillomatosis: eight years of the Cuban national programme.
Deunas L, Alcantud V, Alvarez F, Arteaga J, Benitez A, Bopuza M, Carniege L, Cartaya B, Comas C, Cotayo R, Escobar H, Fernandez H, Fernandez M, Fernandez R, Garcia M, Iznaga N, la O F, Marquez J, Nordet D, Perez J, Quintero J, Redonavich A, Robeleco M, Rodriguez H, Strander H, et al
Otorhinolaryngology Services of Hospitals throughout Cuba, Ministry of Public Health, Havana, Cuba.
Unique Identifier: 97226908
Laryngeal papillomatosis is one of the first diseases where interferon (IFN) was found to be effective. In 1983, a programme for the treatment of all such cases started in Cuba. Up to December 1991, 125 patients (92 children, 33 adults) have been treated: 102 with leucocyte IFN-alpha, 12 with recombinant IFN-alpha-2b, and 11 have received both preparations. Case management consisted of surgical removal of the lesions followed by an IFN schedule starting with 10(5) IU/kg of weight in children or 6 x 10(6) IU in adults, i.m. daily. The dose was progressively reduced, as long as no relapses occurred. At the end of the one-year schedule the doses were reduced to 5 x 10(4) IU/kg in children or 3 x 10(6) IU in adults, weekly. If there was a relapse, it was removed surgically and the patient returned to a higher dose level. Most cases (89; 71 per cent) have not relapsed after the treatment; 60 of them have been followed for more than three years. In those with relapses, the frequency of recurrence decreased in all but four patients. The treatment seemed to be more effective if initiated less than three months after the disease onset. The tracheostomy could be removed in five out of seven patients who needed it before the IFN treatment and was necessary in only three new cases during IFN treatment. In two of these, decannulation was possible later on. In a total of 14 patients relapses persisted after several cycles of IFN treatment. They were considered resistant to such treatment. No severe side effects were reported. The most frequent ones were fever, drowsiness, increased bronchial secretion, chills and headache. The establishment of this programme has maintained the disease under control in Cuba.
Anticancer Res 1997 Jan;17(1A):307-311
Detection and analysis of human papillomavirus 16 and 18 homologous DNA sequences in oral lesions.
Wen S, Tsuji T, Li X, Mizugaki Y, Hayatsu Y, Shinozaki F
Department of Oral and Maxillofacial Surgery, Yamaguchi University School of Medicine, Ube, Japan.
Unique Identifier: 97219369
The prevalence of human papillomavirus (HPV) 16 and 18 was investigated in oral lesions of the population of northeast China including squamous cell carcinomas (SCCs), candida leukoplakias, lichen planuses and papillomas, by southern blot hybridization with polymerase chain reaction (PCR). Amplified HPV16 and 18 E6 DNA was analyzed by cycle sequence. HPV DNA was detected in 14 of 45 SCCs (31.1%). HPV18 E6 DNA and HPV16 E6. DNA were detected in 24.4% and 20.0% of SCCs. respectively. Dual infection of both HPV 16 and HPV 18 was detected in 6 of 45 SCCs (13.3%), but not in other oral lesions. HPV 18 E6 DNA was also detected in 2 of 3 oral candida leukoplakias, but in none of the 5 papillomas. Our study indicated that HPV 18 infection might be more frequent than HPV 16 infection in oral SCCs in northeast Chinese, dual infection of high risk HPV types was restricted in oral SCCs, and that HPV infection might be involved in the pathogenesis of oral candida leukoplakia.
Carcinogenesis 1997 Feb;18(2):377-381
Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multiorgan carcinogenesis model.
Kim DJ, Han BS, Ahn B, Hasegawa R, Shirai T, Ito N, Tsuda H
Chemotherapy Division, National Cancer Centre Research Institute, Chuo-ku, Tokyo, Japan.
Unique Identifier: 97207139
The modification potential of indole-3-carbinol (I3C), a naturally occurring compound found in cruciferous vegetables, on neoplastic development was assessed using a rat medium-term multiorgan carcinogenesis model. One-hundred male Sprague-Dawley (SD) rats were randomly divided into three groups and sequentially treated with diethylnitrosamine (DEN; 100 mg/kg b.w., a single i.p.), N-methyl-N-nitrosourea (MNU; 20 mg/kg b.w., four times i.p., at days 5, 8, 11 and 14), and dihydroxy-di-N-propyl-nitrosamine (DHPN; 0.1% in the drinking water during weeks 1 and 3) (DMD treatment; groups 1 and 2) or the vehicles alone (group 3) in the first 3-week initiation period. Animals of groups 1 and 3 were then given diet containing 0.25% I3C from week 4 until week 24, followed by a return to basal diet for 28 weeks, and subgroups were killed at weeks 24 and 52. I3C caused significant increases in both number (no./cm2) and area (mm2/cm2) of glutathione S-transferase placental form (GST-P)-positive liver cell foci assessed at week 24 of the experiment (P<0.01, 0.001). The incidence of hepatocellular adenomas in the DMD and I3C group at week 52 showed a tendency for elevation as compared to the DMD alone group, but this was not statistically significant. The thyroid gland tumour incidences in the DMD and I3C groups were significantly increased compared with the DMD alone group values at week 52 (P<0.01). In conclusion, I3C enhanced liver and thyroid gland neoplastic development when given during the promotion stage in the present rat medium-term multiorgan carcinogenesis model.
J Environ Pathol Toxicol Oncol 1995;14(3-4):193-196
Association of herpes simplex virus type-I and human papilloma virus with carcinoma of the oral cavity and oropharynx.
Ahmed S, Jafarey NA
Department of Pathology, Ayub Medical College, Abbottabad, Pakistan.
Unique Identifier: 97157412
This study consists of 56 carcinoma cases of the oral cavity and oropharynx, 56 controls matched for age, sex, and habits, and 100 other controls proportionate to the population of Karachi. Biopsy material of the carcinoma cases and oral smears of the two control groups were negative for HSVI and HPV with peroxidase-antiperoxidase staining. The Enzyme Immunosorbent assay (EIA) of sera revealed significantly high levels of anti HSV-I IgG and IgM antibodies in carcinoma cases (96.43% and 25.00%, respectively) when compared with matched controls (73.21% and 3.5%, respectively).
J Photochem Photobiol B 1996 Nov;36(2):183-184
Unusual adverse reaction in a patient sensitized with Photosan 3.
Ofner JG, Schlogl H, Kostron H
ENT-Univ. Clinic. Innsbruck, Austria.
Unique Identifier: 97155558
Serious side effects of photodynamic therapy (PDT) are rare (A.L. Abramson, M.J. Shikowitz, V.M. Mullooly, Clinical effects of photodynamic therapy on recurrent laryngeal papillomas, Arch. Otolaryngology Head Neck Surg., 118 (1992) 25-29; A.L. Abramson, M.J. Shikowitz, Clinical exacerbation of systemic lupus erythematosus after photodynamic therapy of laryngotracheal papillomatosis, Laser Surg. Med., 13 (1993) 677-679). The most frequent side effects of PDT are hypersensitive skin reactions, local edema, nausea, a metallic taste and liver-toxicity (J. Feyh, E. Kastenbauer, Treatment of laryngeal papillomatosis with photodynamic laser therapy, Laryngorhinootologie, 71 (1992) 190-192; J. Feyh, R. Gutmann, A. Leunig, Die Photodynamische Therapie im Bereich der Hals-, Nasen-, Ohrenheilkunde Laryngorhinootologie, 72(6) (1993) 273-78; M.S. Kavuru, A.C. Mekta, Treatment of recurrent respiratory papillomatosis, N. Engl. J. Med., 326 (1992) 204-205; B.L. Wenig, D.M. Kurtzmann, Photodynamic therapy in the treatment of squamous cell carcinomas of the head and neck, Arch. Otolaryngol Head Neck Surg., 116 (1990) 1267-1270). In this case a patient (aged 57 years) suffering from a recurrent larynx papillomatosis was treated with PDT. He was sensitized with Photosan 3 (DHE) 2.5 mg kg-1 body weight, 24 h prior to photoradiation. As a light source, an argon dye laser, operating at a wavelength of 630 nm was used, coupled with a cylindrical light applicator. After treatment the patient was admitted to an intensive care unit for 24 h. 3 h after photoradiation, general urticarial wheals arose, as well as tachycardia and a decrease in blood pressure followed by all the signs of serious anaphylaxis. 1.5 h after treatment with adrenaline and cortisone and stabilization of the cardiac and circulatory situation no more skin lesions were visible.
Jpn J Clin Oncol 1996 Dec;26(6):393-397
Presence of human papillomavirus type 6f in tonsillar condyloma acuminatum and clinically normal tonsillar mucosa.
Tominaga S, Fukushima K, Nishizaki K, Watanabe S, Masuda Y, Ogura H
Department of Otolaryngology, Institute of Cellular and Molecular Biology, Okayama University Medical School.
Unique Identifier: 97154624
An attempt was made to detect human papillomavirus (HPV) in 8 cases of oral papilloma by Southern blot hybridization. HPV type 6 was identified in a case of tonsillar condyloma acuminatum, but neither HPV type 6 nor 11 was found in the 7 other cases of squamous papilloma. The hybridization pattern of the HPV type 6 DNA after digestion with restriction enzymes revealed that the HPV was of the 6f subtype. DNA samples isolated from the condyloma acuminatum, 3 peripheral specimens of clinically normal tonsillar mucosa, a swab sample and saliva from the male patient with this tonsillar condyloma acuminatum were examined further by polymerase chain reaction (PCR). HPV type 6 DNA was detected in the tonsillar condyloma acuminatum and the 3 specimens of clinically normal tonsillar mucosa, but no HPV type 6 DNA was detectable in the normal tonsillar mucosa by Southern blot hybridization using a whole HPV DNA probe. The presence of a small amount of HPV in clinically normal tissue detectable only by PCR suggests latent infection of peripheral tissues with HPV produced from the condyloma acuminatum. Although HPV type 6 DNA was not detectable in the swab and saliva samples of this single case, further study is necessary for the clinical application of preoperative virological diagnosis by PCR using these samples.
Pediatr Clin North Am 1996 Dec;43(6):1385-1401
Recurrent respiratory papillomatosis.
Bauman NM, Smith RJ
Department of Otolaryngology-Head and Neck Surgery, University of Iowa College of Medicine, Iowa City, USA.
Unique Identifier: 97128978
Juvenile-onset recurrent respiratory papillomatosis is a vertically transmitted disease caused by members of the human papilloma virus family. Characterized by the relentless growth of papillomatous lesions of the larynx, recurrent respiratory papillomatosis imposes significant morbidity on patients and strain on their families. Surgical excision of the papillomata remains the mainstay of therapy, but human papilloma virus DNA persists in adjacent, normal-appearing mucosa and likely serves as a reservoir for viral reseeding. Despite multiple adjuvant treatment modalities, a cure for recurrent respiratory papillomatosis remains elusive. Most afflicted patients eventually enter spontaneous remission, but some endure several hundred surgical procedures before this welcome respite.
J Virol 1996 Dec;70(12):8451-8458
Phenotypical characterization of lymphocytes infiltrating regressing papillomas.
Knowles G, O'Neil BW, Campo MS
The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Bearsden, Glasgow, Scotland, United Kingdom.
Unique Identifier: 97126043
Papillomavirus-induced lesions often regress spontaneously in both humans and animals. Papilloma regression is deemed to be due to a cell-mediated immune response, the nature of which is still ill defined, and is accompanied by immune cell infiltrates. To gain further information on the nature and role of the immune cells present in regressing papillomas, we have analyzed biopsies of papillomas induced in the soft palate of cattle by bovine papillomavirus type 4 (BPV-4) and have phenotypically characterized and quantified the lymphocytes present in these lesions. Eleven papilloma biopsies and seven biopsies of noninfected palate were analyzed for the presence of activated CD4+, CD8+, and gamma delta(WC1+) lymphocytes. We found large numbers of lymphocytes in the subepithelial derma of papillomas but not in normal palate tissue; these cellular masses consisted predominantly of CD4+ lymphocytes, with only a few CD8+ and gamma delta(WC1+) lymphocytes, generally positioned at the periphery of these masses. All three subtypes of lymphocytes were found interdigitated with the cells of the basal layer both in papillomas and in normal palate tissue, but while basal layer CD8+ and gamma delta(WC1+) T cells were detected with similar frequencies in papillomas and uninfected palate, basal layer CD4+ T cells were much more frequent in papillomas. CD4+, CD8+, and gamma delta(WC1+) lymphocytes were found in the suprabasal layers of papillomas, but the CD8+ and gamma delta(WC1+) T cells were more numerous and had migrated further into the differentiating keratinocytes of the papilloma fronds than the CD4+ T cells. We conclude that T-cell infiltration is characteristic of regressing BPV-4 papillomas, that CD4+ lymphocytes are specifically and massively recruited into the regressing papillomas, and that although all three lymphocyte subsets can penetrate the papilloma, only the CD8+ and gamma delta(WC1+) lymphocytes are able to migrate into the fronds. These results suggest that all three lymphocyte subsets have an important role to fulfill during natural regression of papillomas.
Rev Alerg Mex 1996 Sep;43(5):133-136
Combined treatment in recurrent laryngeal papillomatosis with CO2 laser microlaryngoscopic resection and interferon alpha 2b
Montero Mora P, Hernandez Colin DD, Enriquez Palomec O, Mejia Ortega J
[Article in Spanish]
Servicio de Inmunologia Clinica y Alergia, Hospital de Especialidades Dr. Bernardo Sepulveda, Centro Medico Nacional Siglo XXI, IMSS.
Unique Identifier: 97122748
Laryngeal papillomatosis of viral origin and bad prognosis is characterized by multiple recurrence that induced obstruction of air pathways. Surgical remove with laser CO2 is the elected treatment and the its combination with interferon (INF) has improved the prognosis of this recurrent viral disease. Here is a presents a preliminary study based upon such therapeutic scheme. Twelve patients diagnosed with laryngeal papillomatosis; 6 women and 6 men from 32 to 72 years of age were included into two therapeutic schemes: Group B, Combined: One woman and 5 men to whom the surgical procedure was followed by a initial local dose of 3 x 10(6) IU of INF alpha 2b (Intron A) and subsequently 10 X 10(6) (of the same INF were administered intramuscular every days during 15 months the statistical analysis (Fisher test) between patients of the both groups of treatment showed a significant (p < 0.0001) clinical improvement of the patients who received the combined treatment (B). In this group of patients was found incidence of the collateral effects such as: headache, fever arthralgias, depression and anorexia.
Acta Otorrinolaringol Esp 1996 Jul;47(4):306-310
Papillomas in otorhinolaryngology: clinics, diagnostics and treatment.
Lopez Amado M, Lozano Ramirez A, Labella Caballero T
Catedra de ORL, Facultad de Medicina, Santiago de Compostela (La Coruna).
Unique Identifier: 97119106
The clinical, diagnostic, and therapeutic features of 257 papillomas of the ear, nose and throat were studied. These tumors were found in a population of about 500,000 inhabitants over a 20-year period (1973-1992). The clinical manifestations of papillomas were varied and more dependent on location than on the size or number of lesions. The most frequent symptom was a foreign body sensation. Twenty-four percent of cases were asymptomatic and the diagnosis was made during a general physical examination; such diagnoses were most frequent in the pharynx. The mean duration of symptoms before visiting a physician was 10 months (longer in papilloma of the oral cavity and shorter in the pharynx). The initial clinical diagnosis was correct in 63% of cases. Lesions of the oral cavity presented most diagnostic problems and those of the pharynx the least. A clinical diagnosis of cancer was made most often in the larynx. Treatment was surgical in every case. Twenty percent required more than one operation to remove the papilloma.
Arch Otolaryngol Head Neck Surg 1996 Dec;122(12):1404-1408
Association of human papillomavirus type 11 DNA with squamous cell carcinoma of the tongue.
Fife KH, Fan L, Fritsch MH, Bryan J, Brown DR
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Unique Identifier: 97115360
A 47-year-old man with a history of a benign papilloma of the tongue 5 years earlier was treated for a squamous cell carcinoma of the tongue with surgical resection. An analysis of the tumor DNA using several methods showed the presence of human papillomavirus (HPV) type 11 sequences that migrated with the high molecular weight cellular DNA, suggesting integration of viral DNA into the cellular genome. A segment of the HPV DNA was cloned from the lesion and shown to be similar to prototype HPV 11 DNA, except for some variability in the viral long control region. The proviral DNA contained part of the L1 region, all of the viral long control region, the entire E6 and E7 open-reading frames, and at least a portion of the E1 region; the E4 region appeared to be deleted. The integration sites of the HPV DNA could not be specifically identified. An analysis of the p53 tumor suppressor gene region of the tumor DNA showed no evidence of mutation. These results suggest that the HPV 11 DNA may have had a role in the origin of the cancer in this patient.
Rhinology 1996 Sep;34(3):184-185
An expansive papilloma of the nasolachrymal drainage system harbouring human papilloma virus.
Buchwald C, Skoedt V, Tos M
Department of Otolaryngology, Gentofte University Hospital, Copenhagen, Denmark.
Unique Identifier: 97093329
We report a case of an expansive tumour extending from the lachrymal sac into the adjacent maxillary sinus. Histology showed a benign exophytic papilloma. By means of the in situ (DNA) hybridization technique, human papilloma virus (HPV) 6/11 were demonstrated, indicating a viral aetiology, similar to exophytic papillomas of the nose and larynx.
Anticancer Res 1996 Sep;16(5A):2709-2712
Effects of 1,4-phenylenebis(methylene)selenocyanate, phenethyl isothiocyanate, indole-3-carbinol, and d-limonene individually and in combination on the tumorigenicity of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung.
el-Bayoumy K, Upadhyaya P, Desai DH, Amin S, Hoffmann D, Wynder EL
American Health Foundation, Valhalla, NY 10595, USA.
Unique Identifier: 97074948
In this study we examined whether chemopreventive agents that had each been shown to be effective against lung tuorigenesis induced in A/J mice by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were more effective when applied together as a "cocktail" than as individual compounds. Groups of A/J mice were fed a diet containing 1,4-phenylenebis(methylene)selenocyanate (p-XSC; 5 ppm as selenium, 0.0005%), phenethyl isothiocyanate (PEITC; 0.008%), indole-3-carbinol (I3C; 0.18%), d-limonene (d-L, 0.63%), or a mixture of all four at the above levels. Mice were fed experimental diets (AIN-76A plus a chemopreventive agent, or a mixture of the four chemopreventive agents) for 17 weeks. One week after beginning the experimental diets, the animals received a single i.p. injection of 10 mumol NNK (2.07 mg) in 0.1 ml saline. Sixteen weeks after the NNK application the bioassay was terminated. Dietary p-XSC, PEITC, I3C, d-L, and their admixture reduced significantly the number of lung tumors per mouse from 8.1 in the positive control to 3.2, 3.7, 4.9, 2.4, and 2.5, respectively (p < 0.05). The inhibition of lung tumor multiplicity in mice fed either the mixture or d-L alone was also significantly stronger than in those fed the diet containing only I3C. However, neither individual agents nor their mixture had a measurable effect on lung tumor incidence. Although the effect of the mixture on lung tumor incidence in this assay remained imperfect, this preliminary investigation provides some basis for the future design of chemoprevention studies.
Br J Cancer 1996 Nov;74(9):1482-1486
A phase I clinical trial of imiquimod, an oral interferon inducer, administered daily.
Savage P, Horton V, Moore J, Owens M, Witt P, Gore ME
Department of Medicine, Royal Marsden Hospital, London, UK.
Unique Identifier: 97069566
Imiquimod is an orally active interferon inducer with anti-tumour activity in experimental animals. In this study the tolerability, toxicity and biological effects of daily oral imiquimod administration were investigated in 21 patients with refractory cancer. Patients were treated with doses of 25 mg, 50 mg, 100 mg or 200 mg on a projected 112 day course. Only three patients completed the course, all at the 50 mg dose. Treatment toxicities were dose related and mainly comprised flu-like symptoms, nausea and lymphopenia. Of the 21 patients, five received dose reductions and in five treatment was discontinued because of treatment-related toxicity. The biological activity of imiquimod was confirmed by significant and sustained rises in peripheral blood mononuclear cell (PBMC) 2-5A synthetase (2-5AS) levels at all doses. At 100 mg and 200 mg these occurred within the first 24 h of administration. Levels of neopterin and beta 2-microglobulin (beta 2M) were also significantly elevated when assessed after three weeks' treatment. Interferon production was not demonstrated within the first 24 h of the initial dose but, following repeated doses, ten of the patients developed detectable serum interferon concentrations with a maximum value of 5600 IU ml-1 recorded. Administration of imiquimod did not have any significant effect on serum levels of tumour necrosis factor (TNF) or interleukin 1 (IL-1), nor did it lead to development of detectable levels of antibodies to interferon. One mixed clinical response was observed after 4 weeks' treatment at 100 mg in a patient with renal cell cancer. Daily administration of imiquimod causes activation of the interferon production system but at higher doses results in unacceptable toxicity. Further investigation of imiquimod as an interferon-inducing agent in cancer patients is suggested at either the lower dose levels or employing alternative dosing schedules.
AJ Interferon Cytokine Res 1996 Sep;16(9):739-743
Modulation of human papillomavirus type 16 mRNA in cervical invasive carcinoma patients by interferon-alpha therapy.
Garcia-Milian R, Rios MA, Amigo M, Diaz D, Guilar O, Silveira M, Arana MJ, Perea SE
Departamento de Biologia Celular, Centro de Investigaciones Biologicas, Ciudad Habana, Cuba.
Unique Identifier: 97041788
Mechanisms by which interferon produces papilloma regression remain largely unknown. We analyzed biopsies from three cervical invasive carcinoma patients treated with interferon-alpha (IFN-alpha) administered both topically and i.m. for 15 days. All specimens contained human papillomavirus (HPV-16) DNA as determined by polymerase chain reaction using specific HPV-16 E7 primers. Interestingly, in two patients. HPV-16 mRNA expression was reduced (44% and 67%, respectively) after IFN treatment. Upregulation of 2-5 A synthetase and PKR mRNA levels were indicative of the IFN effect. A larger study should be initiated to see whether IFN-alpha modulates the HPV-16 mRNA levels in tumor biopsies from cervical carcinoma patients.
Drug Metab Dispos 1996 Sep;24(9):927-931
Dietary indole-3-carbinol inhibits FMO activity and the expression of flavin-containing monooxygenase form 1 in rat liver and intestine.
Larsen-Su S, Williams DE
Toxicology Program, Oregon State University, Corvallis 97331-6602, USA.
Unique Identifier: 97041329
Indole-3-carbinol (I3C), a naturally occurring component of cruciferous vegetables, has been shown to be an effective cancer chemopreventative agent in a number of animal models, and is currently being evaluated in human clinical trials. One proposed mechanism of action for I3C involves binding of I3C acid condensation products (formed in the stomach) to the Ah receptor, with resultant induction of both Phase I and Phase II enzymes. We have previously shown that dietary administration of I3C to male Fischer 344 rats markedly induces hepatic levels of CYP1A1, and to a lesser degree CYP1A2, CYP2B1/2, and CYP3A1/2. We now report that such treatment concurrently inhibits both the activity and expression of flavin-containing monooxygenase (FMO) form 1 in rat liver and intestine. This inhibition demonstrates both a time and dose dependency, resulting in an 8-fold reduction in expression of FMO1 in liver, and almost total ablation of FMO1 in intestinal tissues at the highest dietary I3C levels examined. There are many examples of xenobiotics that are metabolized by both the CYP and FMO monooxygenase systems. In many cases these enzyme systems produce different metabolites, which often have strikingly disparate toxicological and/or therapeutic properties. Therefore, the marked shift in the ratio of FMO/CYP levels in the livers (and other tissues) of rats fed I3C may result in significant alterations in the metabolism, disposition, and toxicity of xenobiotics. Testing for a similar phenomenon in humans would seem advisable before wide-spread administration.
Int J Pediatr Otorhinolaryngol 1996 Mar;35(1):31-38
Role of cesarean section in prevention of recurrent respiratory papillomatosis--is there one?.
Kosko JR, Derkay CS
Department of Otolaryngology--Head and Neck Surgery, Eastern Virginia Medical School, Norfolk 23507, USA.
Unique Identifier: 97041329
Recurrent respiratory papillomatosis (RRP) is a benign yet aggressive neoplasm that produces considerable morbidity in children. Previous studies have linked RRP in children to mothers with genital tract human papillomavirus infections (HPV). Risk factors for vertical transmission have not been well identified. Controversy exists among obstetricians and otolaryngologists regarding the role of cesarean section in preventing the transmission of HPV disease from mother to child. We address this issue by presenting the results of a national survey of otolaryngologists, the American College of Obstetrics and Gynecology position statement, the relevant literature regarding the association between RRP and maternal HPV, and the proposed mechanisms for HPV transmission at birth. We postulate a very limited role for cesarean section in preventing transmission of RRP, given our present knowledge of this disease.
Virus Genes 1996;12(2):165-178
Characterization of human papillomavirus type 57b: transforming activity and comparative sequence analysis as probes for biological determinants associated with high-risk oncogenic viruses.
Trujillo JM, Wu TC, Mounts P
Department of Molecular Microbiology and Immunology, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Unique Identifier: 97033386
The association of human papillomavirus type 57 (HPV-57) with premalignant and malignant tumors of the nasal cavity was previously reported (Wu et al., Lancet 341, 522, 1993). We determined the complete nucleotide sequence of HPV-57b (GenBank 37537), which was molecularly cloned from a benign fungiform papilloma, and compared it with other HPV types and HPV-57a, which was cloned from an inverted papilloma of the maxillary sinus by de Villiers et al. (Virology 171, 248. 1989). Comparative and phylogenetic analysis of amino acid sequences of the HPV-57b oncogenes E5, E6, and E7 were performed with HPV-6, 11, 16, and 18. Phylogenetic trees using the Jotun-Hein algorithm indicated a closer relationship of HPV-57b E5 and E7 with corresponding genes of HPV-18. Signature pattern analysis of these two oncogenes was also in agreement with a closer relatedness to HPV-16 and 18 oncogenes, which are associated with a high risk for malignant progression. Compared with 7861 bp of HPV-57a, HPV-57b had 7868 bp as well as differences in the restriction enzyme sites and the open reading frames, including at least five additional ones. To investigate the oncogenic potential of HPV-57b, NIH 3T3 and REF52 cells were cotransfected with two plasmids: pKP54. HPV-57b, which contains the HPV-57b genome, and pMT.neo.1, which confers resistance to G418. After selection in culture medium containing G418, 58% of the G418r NIH 3T3 colonies and 47% of the G418r REF52 colonies exhibited morphological transformation. These results indicate that the transcriptional regulatory elements and the oncoproteins of HPV-57b are active in vitro to induce cellular transformation, as are other high-risk HPV types.
Clin Otolaryngol 1993 Dec;18(6):470-474
Human papillomavirus in laryngeal papillomas and in adjacent normal epithelium.
Rihkanen H, Aaltonen LM, Syrjanen SM
Department of Otolaryngology, Helsinki University Central Hospital, Finland.
Unique Identifier: 97031297
Eleven adults with laryngeal papillomas were studied for the presence of human papillomavirus (HPV) DNA by in situ hybridization. As well as from the papillomas, three additional biopsies were taken from the normal-appearing mucosa as follows: the involved vocal cord, the opposite vocal cord (when the papilloma was unilateral), and from the ventricular fold on the side of the lesion. These normal tissues were analysed by polymerase chain reaction (PCR) to detect HPV DNA. All except one of the 11 papillomas contained HPV DNA; nine were HPV 6/11 DNA positive and one positive for HPV 16 DNA. The normal-appearing laryngeal mucosa harboured HPV DNA in eight out of 11 patients. The present results strongly support the concept that the adult-type laryngeal papilloma is an HPV-induced lesion, mostly due to HPV types 6 and 11. The persistence of HPV DNA in the adjacent normal epithelium is consistent with the frequent recurrence of these lesions.
Nutr Cancer 1996;26(2):203-208
Suppression of mouse skin papilloma by canthaxanthin and beta-carotene in vivo: possibility of the regression of tumorigenesis by carotenoids without conversion to retinoic acid.
Katsumura N, Okuno M, Onogi N, Moriwaki H, Muto Y, Kojima S
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
Unique Identifier: 97029547
Using mouse skin papilloma as a model system, we examined whether the antitumorigenic activity of carotenoids was related to their provitamin A activity. Oral administration of canthaxanthin (CX) or beta-carotene at 200 mg/kg/day for 14 days significantly reduced the cumulative size of papillomas induced on the skin by 9,10-dimethyl-1,2-benzanthracene (p < 0.05), after the accumulation of these carotenoids in the tumors. The levels of a protooncogene, c-myc, were simultaneously suppressed in papillomas in carotenoid-treated mice. Because CX cannot be converted metabolically to retinoids, these results suggested that CX directly inhibited the growth of papillomas. Neither the accumulation of retinoids nor the expression of a retinoic acid-inducible gene, retinoic acid receptor-beta, was found in papillomas of CX- and beta-carotene-treated mice, suggesting that, like CX, beta-carotene might exert the tumor-suppressing effect without being converted to retinoids. Thus a certain antitumorigenic activity of carotenoids appears not necessarily to require their provitamin A activity.
Nutr Cancer 1996;26(2):149-157
Dietary conjugated linoleic acid modulation of phorbol ester skin tumor promotion.
Belury MA, Nickel KP, Bird CE, Wu Y
Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47907, USA.
Unique Identifier: 97029542
The fatty acid derivative conjugated dienoic linoleate (CLA) has been shown to inhibit initiation and postinitiation stages of carcinogenesis in several experimental animal models. The goal of the present study was to determine the role of increasing levels of dietary CLA in mouse skin tumor promotion elicited by 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice were fed control (no CLA) diet during initiation, then switched to diets containing 0.0%, 0.5%, 1.0%, or 1.5% (wt/wt) CLA during skin tumor promotion by TPA. Body weights of mice fed 0.5%, 1.0%, or 1.5% CLA were similar to each other but were significantly lower (p < 0.05) than weights of mice fed no CLA (0.0%) throughout promotion. A reduction in papilloma incidence was observed in mice fed 1.5% CLA from Weeks 8 to 24 compared with mice fed diets containing 0.0-1.0% CLA (p < 0.05). Twenty-four weeks after tumor promotion was begun, diets containing 1.0% and 1.5% CLA inhibited tumor yield (4.94 and 4.35 tumors/mouse, respectively) compared with diets without CLA (0.0% CLA, 6.65 tumors/mouse, p < 0.05) or 0.5% CLA (5.92 tumors/mouse, p < 0.05). These data indicate that CLA inhibits tumor promotion in a manner that is independent of its anti-initiator activity. Further studies are warranted in identifying cellular mechanisms that are likely to be involved with the antipromoter effects of CLA.
Obstet Gynecol Clin North Am 1996 Sep;23(3):699-706
Recurrent respiratory papillomatosis.
Kashima HK, Mounts P, Shah K
Department of Otolaryngology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Unique Identifier: 97023594
Recurrent respiratory papillomatosis is an uncommon clinical disorder of the respiratory epithelium caused by HPV. It shares an identical viral etiology with genital condyloma and, in all likelihood, is transmitted at the time of birth (juvenile onset RRP) or through intimate sexual contact (adult onset RRP). Despite the precision of the surgical laser under magnification of the operating microscope, a substantial proportion of patients with RRP, adults as well as pediatric, require repeated operations at frequent intervals because of severe hoarseness and upper airway obstruction. For the management of at least a subset of patients, the efficacy of adjuvant agents (interferon is a leading choice) should be investigated in a multi-institutional clinical trial. For the potential prophylactic benefit, cesarean sections in selected high-risk expectant mothers should be considered.
Respir Med 1996 Jan;90(1):53-55
Recurrent respiratory papillomatosis with malignant transformation in a young adult.
Orphanidou D, Dimakou K, Latsi P, Gaga M, Toumbis M, Rasidakis A, Jordanoglou J
Respiratory Medicine Department, School of Medicine, Athens University, Greece.
Unique Identifier: 97010266
The term 'papilloma' was first used by Mackenzie 100 years ago, who claimed that this was the most benign tumour of the larynx. Today papillomas are considered to be caused by the Human Papilloma Virus group (H.P.V.). The majority of patients suffering from this disease which is also referred to as 'recurrent respiratory papillomatosis' require multiple surgical operations for tumour removal. Malignant transformation of papillomas, which is a rare condition, is considered to occur mainly to irradiated patients. The following report describes the case of a male patient, with a history of vocal cord papillomas since his first year of age, who developed bronchial and pulmonary spread of the disease. He died at the age of 26 years because of squamous cell carcinoma which was related to the malignant transformation of the pulmonary papillomas.
Laryngorhinootologie 1996 Jan;75(1):34-37
Brush cytology and HPV detection in chronic laryngitis and papillomatosis.
[Article in German]
Meister EF, Behrendt W, Pustowoit B, Schieck H
Klinik und Poliklinik fur Hals-, Nasen-, Ohrenheilkunde.
Unique Identifier: 97003806
BACKGROUND: We investigated the utility of cytologic studies (including follow-up studies) in our specialty in determining the prevalence of human papillomavirus, specifically in the larynx. We utilized Papanicolaou's method of exfoliative cytology and in situ hybridization of the culture (biotin-marked DNA probes). PATIENTS: 486 patients with chronic hyperplastic laryngitis and 74 patients with papilloma were enrolled in the study. RESULTS: In 198 typings in 132 patients (59 patients with papilloma, 41 with chronic hyperplastic laryngitis, 17 with cancer, and 15 healthy), we found distributions of the individual types that were independent of the diagnosis. Particularly often, we encountered human papillomavirus types 18 and 31 in the presence of dysplasia, human papillomavirus type 16 in the presence of cancer, and type 11 in general. CONCLUSIONS: Cytologic examination and human papillomavirus typing of the culture permit us to define a third risk category in addition to the known risk groups smokers and dysplasia patients. Besides this, cytologic follow-up studies can provide further insight into the behavior of preneoplastic epithelial changes.
Wien Klin Wochenschr 1996;108(2):45-47
A new mode of treatment of human papilloma virus associated anogenital lesions using a nonsteroid estrogen analogue.
Schon HJ, Grgurin M, Szekeres T, Schurz B
Institute of Medical Chemistry, University of Vienna.
Unique Identifier: 96432366
Human papilloma virus (HPV)-induced condylomata acuminata in both sexes, as well as cervical dysplasias were treated locally with an ointment or a cream containing 25 mg clomiphene citrate per gram for a fortnight. The DNA of HPV 6, 11, HPV 16, 18, and HPV 31, 35, 51 was monitored pre- and post-therapeutically using an in situ hybridization assay. The therapeutic response to the drug was demonstrated by the disappearance of condylomata acuminata (100%), HPV DNA in cervical dysplasia (up to 80%), and penile genital warts (75%). Under this therapeutic regimen 78% of all cases treated became negative for the probed HPV. The pharmacological action of the drug was diminished in HPV 16, 18 positive lesions. Clomiphene is shown to be an effective anti-HPV drug.
Laryngoscope 1996 Sep;106(9 Pt 1):1099-1102
Apneic anesthesia with intermittent ventilation for microsurgery of the upper airway.
Weisberger EC, Emhardt JD
Department of Otolaryngology-Head and Neck Surgery, Indiana University Medical Center, Indianapolis 46202, USA.
Unique Identifier: 96420014
Apneic anesthesia with intermittent ventilation (AAIV) has been used in 250 procedures on the larynx and trachea at Indiana University Medical Center since October 1989. Initially employed for laryngeal papilloma removal in children, this anesthetic technique is now used for other procedures and in adult patients. The advantages of AAIV include improved visualization of the airway, absence of combustible material, and lack of vocal cord motion during surgery. No significant complications have occurred with AAIV. The high degree of safety for this anesthetic technique relates largely to the constant monitoring of oxygen saturation using pulse oximetry and the periodic measurement of end-tidal carbon dioxide (CO2) levels. Contraindications to AAIV are age less than 2 years, significant cardiopulmonary disease, and any hypermetabolic state. Relevant pulmonary physiology includes the unique aspects of oxygen and CO2 metabolism in children.
Mod Pathol 1996 Jan;9(1):15-20
Prevalence of human papillomaviruses (HPV) in benign and malignant tumors of the upper respiratory tract.
Shen J, Tate JE, Crum CP, Goodman ML
Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, USA.
Unique Identifier: 96419177
The role for human papillomavirus (HPV) in head and neck tumors is not established. To evaluate the possible role of HPV in head and neck neoplasms, 22 cases of laryngeal squamous papilloma (LP), 32 cases of laryngeal squamous cell carcinoma (LSCC), 40 cases of nasal inverted papilloma (NIP), 14 cases of nasal squamous cell carcinoma (NSCC), and 40 cases of nasopharyngeal carcinoma (NPC) were evaluated for the presence of HPV DNA using the polymerase chain reaction (PCR) with two sets of primers in separate reactions: HPV-L1 consensus primers, HPV16 and HPV18 E7 primers for HPV nucleic acid detection. Restriction fragment length polymorphism of L1 PCR product was used for typing of HPV. Overall, HPV DNA was detected in 18 of 22 cases (81.8%) of LP, 3 of 32 cases (9.4%) of LSCC, 17 of 40 cases (42.5%) of NIP, 3 of 14 cases of NSCC (21.4%), and none of 40 cases of NPC. HPV6 was found more frequently in LP and HPV11 in NIP (P < 0.001). In the three HPV positive LSCCs, two cases had previous LP and were HPV6 and HPV11 positive, as were the prior papillomas. One other case was HPV18 positive. Only HPV16 was found in the NSCC patients. There was no significant difference in the index of HPV positivity between the NSCC cases associated with (16.7%) and without NIP (25.6%). Our results suggest that HPV plays a role in the development of both LP and NIP, and that similar viral types (i.e., HPV6 and HPV11) may exhibit relative differences in their tissue specificity. HPV appears to be of limited importance as a co-factor in LSCC and NPC lesions, indicating differences in the pathogenesis between papillomas and carcinomas in the upper respiratory tract.
Vestn Otorinolaringol 1996 Jul;4:34-37
Use of transcatheter high-frequency artificial ventilation of the lungs in surgical treatment of obturating papillomatosis of the larynx and trachea in children.
[Article in Russian]
Kolomenskii EE, Leskin GS, Zenger VG, Ashurov ZM
Unique Identifier: 96407698
Investigations of transcatheter high-frequency artificial ventilation of the lungs (THFAVL) in surgical treatment of obturating papillomatosis in children led the authors to the conclusion that this method is optimal in assisting breathing in operative intervention on the larynx. THFAVL is not feasible unless adequate expiration is provided. Hence, the high-frequency regimen must be acquired gradually under control of blood gases in parallel with reopening of rima glottidis with consideration of individual clinical situation. The most effective parameters of the above surgery are: P-1 kgs/cm 2; heart rate under 80 per minute; inhalation/expiration ratio 1:3, 1:4. The emergence of side effects can be prevented in coordinated actions of the surgeon and anesthesiologist.
Vestn Otorinolaringol 1996 Jul;4:32-33
Experience in the use of viferon suppositories in young children with juvenile respiratory papillomatosis.
[Article in Russian]
Onufrieva EK, Malinovskaia VV, Maslova IV, Nurmukhametov RKh, Kol'tsov VD
Unique Identifier: 96407697
The authors tried a new medical form of interferon, rectal suppositories viferon, to treat severe juvenile respiratory papillomatosis in young children. Side effects were absent, antibodies to interferon in low titers were registered in 2 patients only. Further studies are needed to specify the promising effects of the above treatment.
Vestn Otorinolaringol 1996 Jul;4:28-31
Indicators of resistance to infection in children with respiratory papillomatosis.
[Article in Russian]
Ashurov ZM, Savitskaia KI, Rusanova EV, Shevtsov VV, Vozhagov VV, Musatenko LIu
Unique Identifier: 96407696
The study was made of microbiological and immunological aspects of antiinfectious resistance (AIR) in children with respiratory papillomatosis (RP). At admission to hospital RP patients exhibited dysbacteriosis of the upper respiratory tract and colon. Immunological and microbiological response to the infection recurrences was adequate. Interrelated immunological and microbiological indices in RP objectively reflect the course of the pathological process and may be used in objective assessment of the disease and choice of its treatment.
Vestn Otorinolaringol 1996 Jul;4:25-27
Assessment of the formation of antibodies to interferon in patients with juvenile respiratory papillomatosis on interferon therapy.
[Article in Russian]
Kol'tsov VD, Chireshkin DG, Onufrieva EK, Nurmukhametov RKh, Malinovskaia VV, Ershov FI
Unique Identifier: 96407695
Children with juvenile respiratory papillomatosis given alpha 2-INF had antibodies to alpha 2-INF in 67.7% of cases. In children treated with intramuscular recombinant alpha 2-INF (reaferon) alone antibodies to INF occurred in 92.3% of patients. The proportion of such patients fell to 28.5% if the children used recombinant alpha 2-INF as rectal suppositories viferon. The level of the antibodies in 4-48 hours decreased 2 times maximally and returned to the baseline on day 3 since intramuscular injection of alpha 2-INF. It is stated that interferon therapy had a positive effect on juvenile respiratory papillomatosis. Antibodies to INF had no negative effects on the treatment results.
Vestn Otorinolaringol 1996 Jul;4:22-24
Hormonal-metabolic and immune status in recurrent laryngeal papillomatosis in children.
[Article in Russian]
Taresov DI, Lazarev VN
Unique Identifier: 96407694
Clinical, biochemical and immunological findings in 12 children with recurrent laryngeal papillomatosis evidence for defects in hormonal--metabolic and immune profiles in terms of depressed sympathoadrenal, adrenocortical functions and secondary immunodeficiency. To correct the above disorders it is advisable to practice immunocorrective therapy and drugs (prospidin) stimulating adrenal function.
Vestn Otorinolaringol 1996 Jul;4:19-21
Current aspects and prospects of the combined treatment of respiratory papillomatosis in children.
[Article in Russian]
Zenger VG, Ashurov ZM, Selin VN, Shevtsov VV, Vozhagov VV
Unique Identifier: 96407693
Treatment methods and outcomes have been analyzed for 313 children aged 9 months-14 years with respiratory papillomatosis (RP) admitted to ENT clinic in 1950-1995. Beginning from 1982 papillomas were removed by means of ultrasonic disintegration. A novel approach included extracorporeal detoxication and immunocorrection. 85% of patients responded to treatment with discrete plasmapheresis and T-activin. It is concluded that best treatment results were achieved in combination of conventional methods with advanced modalities such as extracorporeal detoxication and immunocorrection.
Vestn Otorinolaringol 1996 Jul;4:12-14
Use of immunomocorrection in the combined treatment of laryngeal papillomatosis in children.
[Article in Russian]
Savenko IV, Tsvetkov EA
Unique Identifier: 96407691
Original immunological studies allowed the authors to design a combined treatment of laryngeal papillomatosis (LP) with administration of immunomodulators and cytostatics. Surgery was performed on demand. Thymic hormone preparation (T-activin, thymalin, thymogen) and prospidin served as immunomodulators and cytostatic, respectively. To create lymphotropism, prospidin was delivered by means of electrophoresis following subcutaneous introduction of 8--16 U lidase. Sensitivity of patients to thymalin was tested in vitro by thymalin-induced changes in the number of CD2--DR+ lymphocytes. Adjuvant modalities were age-adjusted dibasol as inductor of interferon genesis and adaptogens (eleutherococcal fluid extract, B and C vitamins). Such treatment was given to 39 children. Remission duration increased 1.6--2.6-fold, 6 of 7 children with primary LP achieved persistent remission. Positive changes in immunological indices occurred in 84% of children. The above treatment outcomes support the efficacy of the method in childhood LP.
Vestn Otorinolaringol 1996 Jul;4:3-8
Molecular-biological aspects of juvenile respiratory papillomatosis and its combined treatment.
[Article in Russian]
Gerain V, Chireshkin DG
Unique Identifier: 96407689
Systemic clinical and molecular-biological analyses of cause-effect relations between human papillomatosis virus (HPV) and juvenile respiratory papillomatosis (JRP) disclosed general mechanism of HPV infection initiation and stages of tumor genesis. However, there is no consent on the universal etiopathogenetic approach to the disease treatment. The authors give some results to the disease treatment. The authors give some results of present-day combined treatment of JRP which includes surgical removal of papillomas and modulation of immunity by interferon preparations.
J Med Microbiol 1996 Sep;45(3):162-166
A high prevalence of human papillomavirus DNA in recurrent nasal papillomas.
Ogura H, Fukushima K, Watanabe S
Department of Molecular Genetics, Okayama University Medical School, Japan.
Unique Identifier: 96406854
The prevalence of human papillomavirus (HPV) DNA in nasal papillomas was examined by polymerase chain reaction (PCR) and Southern blot hybridisation. HPV 6 DNA in one case, HPV 57 DNA in one case and HPV 16 DNA in three cases were detected amongst 12 cases of nasal papillomas that comprised three cases of fungiform exophytic papillomas and nine cases of inverted papillomas. Five cases (two exophytic and three inverted papillomas) were recurrent and four (80.0%) of these were HPV DNA-positive. The remaining seven cases were non-recurrent and only one (14.3%) was HPV DNA-positive. This difference in HPV DNA detection rates between recurrent and non-recurrent nasal papillomas was statistically significant.
Minerva Ginecol 1996 May;48(5):199-204
Maternal-fetal transmission of human papillomavirus.
[Article in Italian]
Alberico S, Pinzano R, Comar M, Toffoletti F, Maso G, Ricci G, Guaschino S
Clinica Ginecologica e Ostetrica, Universita degli Studi, Trieste.
Unique Identifier: 96378230
AIM: Human papilloma virus (HPV) infection is one of the most frequently observed sexually-transmitted diseases (10-60% of the general population). In pregnant women, as well as accelerating the evolution of dysplasia to cervical cancer, the infection may be transmitted to the fetus during gestation or at the time of birth. Children who have been infected at birth may develop laryngeal papillomatosis during the first 5 years of life that may, in some cases, spread to the point of causing aphonia or severe respiratory obstruction. There is also the risk, although it is very low, of a carcinomatous degeneration of the larynx in these subjects during adulthood. The hypothesis of the present study was to verify the prevalence of HPV infection in a population of pregnant women and the prevalence of maternal-fetal transmission. EXPERIMENTAL DESIGN: A prospective longitudinal design lasting 11 months was used for the study. It included the collection of an endocervical biopsy from population of pregnant women using a swab that was diluted in 3 cc of physiological solution, and the collection of oropharyngeal secretions from their respective neonates using a cottonwool bud. PARTICIPANTS AND METHODS: A total of 170 pregnant women attending the Obstetric Centre of the Obstetric and Gynecological Clinic of Trieste University were recruited in the study. An endocervical biopsy was taken during the 1st and/or 2nd trimester of gestation and/or at the start of labour. Of these subjects, 23 completed all the planned biopsies and a sample of oropharyngeal secretion was collected from their neonates. TESTS: From the material obtained the presence of HPV-DNA was analysed using a PCR (protein chain reaction) technique consisting of the following steps: 1) culture of human cells expressing sequences of HPV 16 and 18 used as positive controls; 2) preservation of tissue material washed in watery 4% formalin solution; 3) amplification and viral characterization in types 6-11-16-18-31-33-52. RESULTS: Positive HPV-DNA results in at least one of the three samples collected during the various periods of gestation was 31.2%, whilst in the population in which all the planned samples were performed the frequency of positive cases was 30.4%. Positive results for HPV-DNA in oropharyngeal secretions from neonates was 21.7%. The concordance of positivity for HPV-DNA in mothers at the time of labour and in their respective neonates was 57.14%. CONCLUSIONS: The trend of infection did not reveal substantial changes during the various gestational periods in which tests were performed. The possibility of HPV-DNA transmission from mother to fetus is high, above all when the maternal PCR test is positive at the time of birth, or in the presence of a high viral load. This justifies the need to monitor this infection in pregnancy in those affected by florid genital condylomatosis or with koilocytosis on cervical cytology. It is also appropriate to check all HPV-DNA positive neonates one year after birth.
Antiviral Res 1995 Nov;28(3):253-264
Immunomodulating and antiviral activities of the imidazoquinoline S-28463.
Tomai MA, Gibson SJ, Imbertson LM, Miller RL, Myhre PE, Reiter MJ, Wagner TL, Tamulinas CB, Beaurline JM, Gerster JF, et al
Department of Pharmacology, 3M Pharmaceuticals, St. Paul, MN 55144, USA.
Unique Identifier: 96227078
Recently, a new class of immunomodulating agents, represented by the molecules imiquimod and R-842, has demonstrated potent antiviral and antitumor activities in animal models. In this study, another representative of this class, S-28463 (4-amino-2-ethoxymethyl-alpha,alpha-dimethyl-1H-imidazo[4,5-c]quinoline- 1- ethanol) was evaluated for its immunomodulating and antiviral activities. S-28463 induced IFN and other cytokines in vivo in mice, rats, monkeys and in vitro in human peripheral blood mononuclear cell cultures. S-28463 showed potent antiviral activity against herpes simplex virus-challenged guinea pigs when given subcutaneously, dermally, or intravaginally 24 h before infection. Antiviral activity in guinea pigs correlated with the induction of serum 2',5'-oligoadenylate synthetase activity. Thus, S-28463, like the other imidazoquinolines, demonstrates potent antiviral and immunomodulating effects in a number of models.
Int J Dermatol 1995 Sep;34(9):597-606
Antiviral agents in dermatology: current status and future prospects.
Memar OM, Tyring SK
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555, USA.
Unique Identifier: 96073036
The majority of current antiviral agents have become available only during the past decade. The above mentioned antiviral drugs, especially the viral-TK-specific agents have attempted to bring antiviral therapy on par with antimicrobial therapy. The fact, that cells infected with viruses can be selected against the relatively low toxicity to the patient, highlights the present state of antiviral therapy. Since viral infection can be viewed as an integral component of the self (i.e., a condition that cannot simply be surgically eliminated), the science of medicine is turning to the components of the self to overcome such conditions. By administering immune-system-derived agents (e.g., interferons) or compounds that stimulate the immune system (e.g., adjuvants like imiquimod), previously unmanageable conditions become manageable. The future of antiviral therapy will undoubtedly be at the molecular level. With greater understanding of the virus and the immune system with which it interacts, more specific and efficacious antiviral agents will be added to the arsenal of the clinician.
Jpn J Cancer Res 1992 Aug;83(8):835-842
Inhibitory effects of the natural products indole-3-carbinol and sinigrin during initiation and promotion phases of 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.
Tanaka T, Kojima T, Morishita Y, Mori H
First Department of Pathology, Gifu University School of Medicine.
Unique Identifier: 93015230
The modifying effects of indole-3-carbinol (I3C) and sinigrin (SIN) on the initiation and post-initiation phases of tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4-NQO) were investigated in male ACI/N rats. Rats were divided into eight groups: group 1 was given 4-NQO (10 ppm) in the drinking water for 12 weeks, starting at 7 weeks of age; groups 2 and 3 were given 4-NQO and fed the diets containing I3C (1,000 ppm) and SIN (1,200 ppm) for 14 weeks, respectively, starting at 6 weeks of age; groups 4 and 5 were given 4-NQO and then they were fed I3C and SIN containing diets for 23 weeks, respectively, starting one week after 4-NQO exposure; groups 6 and 7 were given I3C and SIN alone, respectively, during the experiment; group 8 served as an untreated control. At the termination of the experiment (week 37), the incidence of tongue neoplasms (squamous cell papilloma and carcinoma) in group 2 (1/15, 7%), group 3 (1/15, 7%), group 4 (3/15, 20%) or group 5 (2/15, 13%) was significantly smaller than that in group 1 (12/17, 71%) (P = 0.0003, P = 0.005 or P = 0.002). No tongue carcinomas developed in rats of groups 2, 3, and 5. Similarly, the incidence of preneoplastic lesions (hyperplasia and dysplasia) of the tongue in group 2 (11/15, 73%), group 3 (10/15, 67%), group 4 (11/15, 73%) or group 5 (10/15, 67%) was significantly lower than that in group 1 (17/17, 100%) (P = 0.04 or P = 0.02). There were no tongue neoplasms in rats of groups 6, 7, and 8. Administration of I3C and SIN also caused significant decreases in the number and area of silver-stained nucleolar organizer regions protein (AgNORs), a new cell proliferation index, of tongue squamous epithelium. Thus, I3C and SIN inhibited rat tongue carcinogenesis in both the initiation and post-initiation phases, when administered in these respective phases together with, or following treatment with, 4-NQO.
Lawrenceville NJ 08648-0643