Winter 1999

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Volume 6 • Number 1

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 (1998 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
Title
Language (if it is not specified assume article is in English)
Author(s)
Primary affiliation (when specified)
Abstract
Unique identifier

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:

Bill Stern
RRP Foundation
P.O. Box 6643
Lawrenceville NJ 08648-0643
(609) 530-1443 or (609)452-6545
E-mail: bills@rrpf.org or rrpf@aol.com

Dave Wunrow
210 Columbus Drive
Marshfield WI 54449
(715) 387-8824
E-mail: wunrowd@tznet.com

Carcinogenesis 1999 (In Press)

Fish Oil Constituent Docosahexaenoic Acid Inhibits Growth of Human Papillomavirus Immortalized Keratinocytes: A Function of Lipid Peroxidation.

Chen, D. and Auborn, K.

Department of Otolaryngology, Long Island Jewish Medical Center, New Hyde Park, NY, USA

The omega-3 PUFAs (polyunsaturated fatty acids) inhibit proliferation of breast cancer cells, whereas omega-6 PUFAs stimulate growth. In this study, we examined effects of PUFA on human precancerous cells. Cervical keratinocytes, immortalized with the oncogenic human papillomavirus (HPV) type 16, were treated with linoleic acid ( an omega-6 PUFA) and the omega-3 PUFAs, eicosapentaenoic acid (EPA)and docosahexaenoic acid (DHA). Using both cell counts and BrdU incorporation, DHA inhibited growth of these cells to a greater extent than EPA whereas linoleic acid had no effect. This effect of DHA was dose-dependent and caused growth arrest. DHA inhibited growth of HPV16 immortalized foreskin keratinocytes and laryngeal keratinocytes grown from explants of benign papillomas caused by papillomavirus, but DHA had no effect on normal foreskin and laryngeal keratinocytes. Indomethacin, a cyclooxygenase inhibitor like DHA, had only minimal effect on growth. DHA inhibited growth in the presence of estradiol, a growth stimulator of these cells.
a -Tocopherol, a peroxiation inhibitor, abrogated effects of DHA implying that DHA effects were via lipid peroxidation.

Unique Identifier: [Not yet assigned]

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Ear Nose Throat J 1998 Dec;77(12):949-50

Endoscopic internal stent: a new procedure for laryngeal webs in the presence of papilloma.

Sataloff RT, Hawkshaw M

Thomas Jefferson University, Department of Otolaryngology-Head and Neck Surgery, Graduate Hospital, Philadelphia, Pennsylvania.

[No abstract available]

Unique Identifier: 99095205

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Ann Otol Rhinol Laryngol 1998 Dec;107(12):1001-5

Flash pump dye laser treatment of laryngeal papillomas.

Bower CM, Waner M, Flock S, Schaeffer R

Department of Otolaryngology-Head and Neck Surgery, Arkansas Children's Hospital, Little Rock 72202, USA.

To evaluate the feasibility and safety of the flash pump dye (FPD) laser for the treatment of laryngeal papillomas, we performed a prospective nonrandomized trial comparing FPD and carbon dioxide (CO2) laser treatment of laryngeal papillomas in a tertiary care children's hospital. Nine patients from 2 to 20 years of age with severe recurrent laryngeal papillomas were enrolled in the study. All patients underwent CO2 laser debulking of papillomas on the left hemilarynx, with 8 W continuous or pulsed energy. The right hemilarynx was treated with the FPD laser with 12 to 77 pulses at 8 to 12 J, through a custom-designed 90 degrees firing fiber. An end point of blanching and purpura of the papillomas was used. The main outcome measures were the safety and ease of operation with the FPD laser, and decreased papilloma size based on visual inspection at 2 weeks postoperative and at the next laser procedure. Seven patients were irradiated I time with an FPD laser, and 2 patients 2 times. No intraoperative complications were noted. One patient developed early postoperative stridor. No patients described more discomfort, and 5 patients described their voice as being the same as or better than it was after prior CO2 laser procedures. Five patients had a 90% or more decrease in size of papillomas on the FPD-irradiated side 2 weeks postoperatively. Three patients had approximately a 50% reduction. A treatment effect was noted in all patients, and was similar to the results noted on the CO2 laser-treated side. Early results with FPD laser treatment of laryngeal papillomas suggest the protocol is relatively safe and feasible. Long-term results are pending. Because the FPD laser coagulates rather than vaporizing tissue, potential advantages may include decreased scarring relative to CO2 laser treatment, and improved patient and operator safety.

Unique Identifier: 99081226

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Auris Nasus Larynx 1998 Dec;25(4):407-12

Long term follow-up study of laryngeal precancer.

Plch J, Par I, Navratilova I, Blahova M, Zavadil M

ORL department Hospital Kolisti, Brno, Czech Republic.

The goal of this study was to determine subsequent malignancy on a discrete group of precancerous laryngeal lesions, and to assess the mortality. In a series of 227 patients, average age 51.8 years (ranging from 13 to 80 years). The changes were followed-up for 12.3 years (minimum of 5 years and maximum of 40 years). 58% are living without any sign of premalignant laryngeal mucosal disease, 13% with controlled precancer, and 3% in remission after surgery for carcinoma. 11% died (9% due to cause unrelated to the cancer) and 15% were lost for follow-up. 17% of the group with mucosal hyper- or metaplasia progressed to mild dysplasia, but none progressed to carcinoma. Reinke's oedema recurred in 4%, no malignancy was observed. Carcinoma developed in 16% of laryngeal papilloma (8% in situ and 8% invasive). 15% of mild dysplasia progressed in severity, but none transformed to malignancy. Moderate dysplasia progressed to severe dysplasia in 12%, carcinoma in situ in 4%. Of cases with severe dysplasia 13% developed in situ carcinoma while 43% progressed to invasive cancer. In the whole series progression to severe grade was seen in 7.1%, and malignant transformation in 4.4%. Three patients (1.3%) died due to subsequent carcinoma. Our results agree with some authors; but the majority of them reports higher incidence of malignant transformation. Invasive carcinoma was diagnosed in the follow-up in seven patients. Those represent only 3% of all laryngeal carcinomas diagnosed in our department in the same period of time. Based on the data we have evaluated the intensity of follow-up in patients with hyperplasia, metaplasia, keratosis and mild dysplasia.

Unique Identifier: 99068554

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Cell Prolif 1998 Jun-Aug;31(3-4):127-38

Differences in C/EBPs in normal tissue and papillomas of the larynx.

Jin L, Yang GY, Auborn K

Department of Otolaryngology, Long Island Jewish Medical Center, The Long Island Campus of Albert Einstein College of Medicine, New York, USA.

Transcription factors belonging to the family of CAAT enhancer binding proteins (C/EBPs) programme differentiation in a wide variety of cells. We asked about the expression of C/EBPs in squamous epithelium. Using immunohistochemistry, C/EBPalpha and C/EBPbeta were easily detected in tissue sections from normal larynx or laryngeal papillomas, benign tumours with a papillomavirus aetiology and characterized by abnormal differentiation. A temporal expression of these C/EBPs occured as keratinocytes differentiated. In both tissues, C/EBPbeta appeared to be exclusively nuclear. In normal tissue, the greatest amount of C/EBPbeta was present in the spinous layer, and much less occurred in the granular layer. The basal layer of the laryngeal papillomas contained the most C/EBPbeta. Less was present in the spinous layer. Little C/EBPbeta was in the granular layer. Much C/EBPalpha was in the cytoplasm in both tissues. In normal tissue, nuclear C/EBPalpha staining was virtually absent in the basal layer, and became present in the spinous layer. Nuclear C/EBPalpha was randomly distributed in all layers in papillomas. Using immunoblots and Southwestern blots, we detected abundant truncated isoforms of C/EBPalpha in the papillomas. Since differentiation of many tissues is determined by the relative amounts of different C/EBPs, our data supports a role for C/EBPs in the differentiation of squamous epithelium.

Unique Identifier: 99068315

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Ear Nose Throat J 1998 Nov;77(11):882-4

Recurrent vocal fold papilloma: resection using cold instruments.

Dean C, Sataloff RT, Hawkshaw M

Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

[No abstract available]

Unique Identifier: 99062893

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Acta Otolaryngol (Stockh) 1998 Sep;118(5):754-8

Detection and typing of human papillomavirus DNA in benign and malignant tumours of laryngeal epithelium.

Garcia-Milian R, Hernandez H, Panade L, Rodriguez C, Gonzalez N, Valenzuela C, Arana MD, Perea SE

Department of Cellular Biology, Center for Biological Research, Hospital Clinico Quirurgico

"10 de Octubre", Havana, Cuba. garcia.milan@cib.cigb.edu.cu

The role of human papillomaviruses (HPV) in laryngeal squamous cell carcinoma has not yet been established. Thirty-three cases of laryngeal squamous cell carcinoma were analysed for the presence of HPV DNA and compared with 25 cases of normal larynx and 29 cases of laryngeal squamous papilloma in their positivity index. The presence of HPV DNA was analysed by using L1 consensus primers and also by primers specific for the E7 gene of HPV types 16 and 18. Four normal laryngeal samples (16%) were positive for HPV DNA against the 24 samples (82%) (p < 0.001) found for laryngeal papilloma and 16 (48.5%) (p < 0.05) found for laryngeal squamous cell carcinoma. HPV 16 was the type most frequently found in laryngeal carcinoma samples. Our results support an etiologic role for this type of HPV in the pathogenesis of laryngeal carcinoma.

Unique Identifier: 99054253

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J La State Med Soc 1998 Oct;150(10):456-9

Recurrent respiratory papillomatosis.

Murray LN, Miller RH

Tulane University Medical School, USA.

Recurrent respiratory papillomatosis is a disease characterized by the growth of wart-like neoplasms anywhere along the aerodigestive tract. The etiologic agent is the human papillomavirus, of which 90 subtypes have been described. The age distribution of those affected appears to be a bimodal curve, with the first peak around 5 years of age and the second occurring in adults in the third decade of life. The mainstay of treatment is surgical resection to maintain an adequate airway; patients often require multiple surgeries. The epidemiology, pathogenesis, clinical features, and treatment options are discussed. Current evidence regarding prognosis and the multifactorial nature of pathogenesis are also reviewed.

Publication Types: Review Review, tutorial

Unique Identifier: 99022709

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Ann Otol Rhinol Laryngol 1998 Oct;107(10 Pt 1):815-9

Significance of DNA ploidy and cell proliferation in juvenile respiratory papillomatosis.

Stern Y, Hurtubise PE, Cotton RT

Department of Pediatric Otolaryngology and Maxillofacial Surgery, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio 45229, USA.

The clinical course of recurrent respiratory papillomatosis (RRP) in children is variable and unpredictable. At present there is no way to identify patients at risk for aggressive disease. The objective of this study was to evaluate whether DNA ploidy and cell proliferation analyses can predict the clinical course in children with RRP. Two different methods of estimating proliferation activity were compared. Nonembedded papilloma biopsy specimens from 18 pediatric patients were analyzed by flow cytometry providing DNA content with cell cycle analysis. The expression of the proliferative marker Ki-67 in papilloma tissue was quantified by immunohistochemistry. The patients were prospectively observed for 12 to 18 months. DNA content analysis and Ki-67 expression were compared to clinical information regarding number of disease sites, distal tracheobronchial spread, number of recurrences, need for tracheostomy, and disease remission. High S-phase fraction, proliferative index, and Ki-67 expression correlated with an aggressive clinical course. DNA ploidy analysis and immunodetection of proliferative markers may assist in predicting prognosis in children with RRP.

Unique Identifier: 99008739

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Biol Pharm Bull 1998 Sep;21(9):993-6

Anti-tumor-promoting activity of diterpenes from Excoecaria agallocha.

Konishi T, Takasaki M, Tokuda H, Kiyosawa S, Konoshima T

Kyoto Pharmaceutical University, Japan.

To search for possible anti-tumor-promoters, we carried out the primary
screening of seventeen diterpenes (1-17) isolated from the resinous wood of
Excoecaria agallocha (Euphorbiaceae) using an in vitro synergistic assay
system. Of these diterpenes, ent-16-hydroxy-3-oxo-13-epi-manoyloxide (5),
(13R,14R)-ent-8alpha,13;14,15-diepoxy-13-epi- labda-3beta-ol (8)
ent-3beta-hydroxy-15-beyeren-2-one (10) and
ent-15-hydroxy-labda-8(17),13E-dien-3-one (14) exhibited significant inhibitory
effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter,
12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, 10 exhibited
remarkable anti-tumor-promoting activity in vivo on a two-stage carcinogenesis
test of mouse tumor using 7,12-dimethylbenz[a]-anthracene (DMBA) as an
initiator and TPA as a promoter.

Unique Identifier: 98453116

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Am J Surg Pathol 1998 Oct;22(10):1291-5

Disseminated mucosal papilloma/condyloma secondary to human papillomavirus.

Bishop JW, Emanuel JM, Sims KL

Department of Pathology, Creighton University School of Medicine, Omaha,

Nebraska, USA.

This report details the histopathologic findings in a woman who acquired the
human papillomavirus 6/11 in her late teens and developed papilloma/condyloma
of the nasopharynx, oropharynx, anogenital region, urethra, and urinary
bladder. General evaluations of immune function reveal no defect, and there was
no evidence of HIV infection. The morphologic expression of HPV 6/11 infection
appears to be completely dependent on the mucosal epithelium affected. The
complete spectrum of benign and premalignant epithelial changes induced by the
human papillomavirus family-papilloma, verrucae, condyloma acuminatum,
epithelial hyperplasia, and dysplasia-were present in this patient with a
single papillomavirus infection. We postulate that this patient has a specific
immune deficiency that limits her ability to control local infection and spread
of the papillomavirus.

Unique Identifier: 98449422

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J Am Acad Dermatol 1998 Oct;39(4 Pt 2):S149-52

Future trends: a new generation of retinoids.

Chandraratna RA

Retinoid Research, Allergan, Inc., Irvine, California 92623, USA.

The existence of several different types of retinoid receptors, response
elements, and cofactors means that retinoid physiology is mediated by multiple
discrete pathways and is highly complex. As a result, non-selective retinoids
have a multitude of physiologic effects and are usually associated with
toxicity problems that limit their therapeutic usefulness. In contrast, because
receptor-selective retinoids have a more focused and targeted action, they are
likely to have a better therapeutic index. Tazarotene is the first of a new
generation of receptor-selective retinoids. Its actions are targeted on 2
retinoic acid receptors (RARs), RAR-beta and RAR-gamma. Current retinoid
research is leading to the development not only of many more novel
receptor-selective retinoids but also of novel types of function-selective
retinoids such as RAR inverse agonists and RAR antagonists. These retinoids are
expected to be of clinical benefit not only in dermatology but also in
oncology, diabetes, and diseases associated with the human papilloma virus.

Unique Identifier: 98449224

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Nutr Cancer 1998;31(2):119-26

Inhibition of skin carcinomas but not papillomas by sphingosine, N-methylsphingosine, and N-acetylsphingosine.

Birt DF, Merrill AH Jr, Barnett T, Enkvetchakul B, Pour PM, Liotta DC, Geisler

V, Menaldino DS, Schwartzbauer J

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, USA. dbirt@iastate.edu

The sphingoid base backbones of sphingolipids are highly bioactive compounds
that affect cell growth, differentiation, diverse cell behaviors, and
programmed cell death. Therefore, the efficacy of sphingosine (SPH) and the
analogs N-acetylsphingosine (NAS), N-methylsphingosine (NMS), octylamine (OCT),
and sterylamine (STR) in the prevention of skin cancer was assessed in female
Sencar mice by measuring effects on the induction of epidermal ornithine
decarboxylase (ODC) activity and hyperplasia by
12-O-tetradecanoylphorbol-13-acetate (TPA) and effects on the induction of skin
tumors by 7, 12-dimethylbenz[a]anthracene (DMBA) and TPA. ODC was measured in
the shaved dorsal skin of mice treated topically with 0.05-20 mumol of these
compounds 30 minutes before application of 8.5 nmol of TPA in 0.2 ml of
acetone. ODC activity was inhibited by > or = 5 mumol of SPH and STR, > or = 10
mumol of NAS and NMS, and 20 mumol of OCT. In contrast, the induction of
hyperplasia was not inhibited by application of these compounds 30 minutes
before TPA. Two carcinogenesis studies were conducted with 10 nmol of DMBA as
the initiator and 3.2 nmol of TPA (2x/wk for 15 wk) as the promoter. In the
first study, NAS, NMS, OCT, and STR (0.05 and 0.5 mumol) were applied before
each TPA application. Papilloma incidence and multiplicity were not inhibited,
but NAS (0.05 mumol) and NMS (0.05 and 0.50 mumol) increased cancer-free
survival. In the second experiment, SPH, NAS, and NMS (0.05 and 0.5 mumol) were
applied 30 minutes before each TPA treatment and twice weekly for 10 weeks
after the final TPA treatment. Papilloma incidence and multiplicity were not
inhibited; however, the proportion of mice without carcinoma was increased by
both doses of SPH and by 0.5 mumol of NAS. Thus low doses of sphingolipids that
were not effective in inhibiting ODC activity, reducing hyperplasia, or
preventing epidermal papilloma development were, nonetheless, effective in
inhibiting carcinoma development.

Unique Identifier: 98443662

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Am J Med Sci 1998 Oct;316(4):285-8

Esophageal papillomatosis from human papilloma virus proven by polymerase chain reaction.

Ravakhah K, Midamba F, West BC

Department of Medicine, Meridia Huron Hospital, Cleveland, Ohio 44112, USA.

Human papilloma viruses (HPVs) are known to infect the genitourinary tract, the
skin, the anal canal, and the upper respiratory tract. Esophageal papillomas
and especially HPV-induced squamous papillomas of the esophagus are rare. The
authors report a case of extensive HPV-induced esophageal polyposis, which was
probably sexually transmitted. The 53-year-old female patient presented with
chronic diarrhea and had occult blood in the stool. She underwent
esophagogastroduodenoscopy, at which time multiple esophageal polyps were
observed and biopsy specimens obtained. Histologic evaluation was consistent
with benign papillomas. Polymerase chain reaction and DNA hybridization of the
biopsied tissue specimens confirmed the diagnosis of HPV infection. Because of
our observation and because of HPV's relationship to cervical and esophageal
cancer, further evaluation of HPV as the cause of esophageal papillomatosis and
as a risk factor for esophageal cancer is warranted.

Unique Identifier: 98437881

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J Invest Dermatol 1998 Oct;111(4):605-8

Efficient expression of naked plasmid DNA in mucosal epithelium: prospective

for the treatment of skin lesions.

Hengge UR, Pfutzner W, Williams M, Goos M, Vogel JC

Department of Dermatology and Venerology, University of Essen, Germany.

Mucocutaneous gene therapy offers exciting new treatment modalities for skin
lesions. Transient expression of naked plasmid DNA could be used as a local
treatment of various skin lesions where the corresponding gene product
(protein) has therapeutic or immunization potential. We analyzed the time
course, magnitude, and histologic expression of the indicator plasmid DNA
(pCMV:beta-Gal) in mucosal epithelium and papilloma lesions. Upon direct
injection of naked plasmid DNA (20 microg) into oral mucosa, expression
occurred at high local concentrations, up to 35-fold higher than in comparable
injections into the epidermis. Due to the accelerated turnover of mucosal
epithelium beta-galactosidase positive epithelial cells were detected in the
basal and suprabasal layers as early as 3 h after injection, whereas only the
most superficial mucosal layers demonstrated beta-galactosidase staining at 24
h post-injection. These biologic characteristics need to be taken into
consideration when clinical applications of expressing naked plasmid DNA in
epithelial tissues are considered.

Unique Identifier: 98435869

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Otolaryngol Pol 1998;52(3):291-7

[Histological and histochemical investigation of pathological laryngeal mucosa

with papillomatosis in children and adults].

[Article in Polish]

Pospiech L, Rak J, Bochnia M, Lesisz I

Katedra i Klinika Otolaryngologii AM we Wroclawiu.

Papillomas of the larynx are the subject of numerous studies. They occur in two
forms (multiple and singular). The authors presented the results of
histological and histochemical investigations of larynx papillomas in 9 adults
and 16 children. The studies comprised patients treated in the Clinic of
Otolaryngology in Wroclaw. Surgically removed lesions constituted the material
for estimation. Peculiar attention was paid to the degree of differentiation of
tumours under the microscope. The interdependence between intensification of
reaction and degree of epithelhyperplasia and strict connection of
intensification of reaction with quantity of dysplastic changes of epithelium
were indicated by estimation of enzymatic reactions. Histological studies
disclosed marked morphological differences between papillomas in children and
adults. The correlation of reactions to lactic dehydrogenase and
NADH2-tetrazole reductase can be treated as an expression of hyperplastic
changes in the epithelium. What is more, the reaction to lactic dehydrogenase
may be regarded as a metabolic index of malignancy.

Unique Identifier: 98433495

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Dev Psychobiol 1998 Sep;33(2):107-23

Thermoregulatory competence and behavioral expression in the young of altricial species--revisited.

Blumberg MS, Sokoloff G

Department of Psychology, University of Iowa, Iowa City 52242, USA.

The behavioral and physiological thermoregulatory capabilities of newborn and
infant mammals have been studied for over half a century. Psychobiologists have
noted that the infants of altricial species (e.g., rats) have physical and
physiological limitations such that heat loss overwhelms heat production, thus
forcing a reliance on behavioral thermoregulation for the maintenance of body
temperature. Recent evidence, however, suggests that a modification of this
view is justified. Specifically, throughout a range of moderately cold air
temperatures, nonshivering thermogenesis by brown adipose tissue contributes
significantly to the infant rat's behavioral and physiological adaptations to
cold challenge. Given the prominent use of altricial species for the study of
infant behavior, increased understanding of the infant's physiological
responses to cold and the effect of thermal factors on behavior is warranted.

Unique Identifier: 98414814

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Laryngoscope 1998 Sep;108(9):1284-90

Dose-related tissue effects of the CO2 and noncontact Nd:YAG lasers in the

canine glottis.

Sullivan CA, Rader A, Abdul-Karim FW, Abbass H, Mohr RM

Department of Otolaryngology-Head and Neck Surgery, Case Western Reserve

University, Cleveland, Ohio, USA.

OBJECTIVES: The CO2 laser is the standard for control of recurrent respiratory
papillomatosis because of its predictable action on laryngeal tissue. The
noncontact neodymium:yttrium aluminum garnet (Nd:YAG) 1064-nm laser is
generally not used in the larynx owing to the lack of data on its tissue
effects, and its potential lack of safety in the larynx. Combined Nd:YAG and
CO2 laser treatments have been used safely in the tracheobronchial tree to
eradicate recurrent respiratory papillomas. The objectives of this study were
to describe and evaluate a method for applying the noncontact Nd:YAG laser to
the larynx, to compare the tissue effects of the Nd:YAG, CO2, and combined
Nd:YAG and CO2 lasers in the canine larynx, and to extrapolate canine tissue
data to the human. METHODS: The CO2, Nd:YAG, and combined Nd:YAG/CO2 lasers
were applied to the glottis in four mongrel dogs. Laryngectomy was performed
and the tissue was examined histologically. The nature and degree of tissue
injury were analyzed relative to laser type and energy data. RESULTS: In the
canine larynx, the CO2 laser vaporized the surface epithelium and caused
varying degrees of edema and necrosis of the lamina propria. The Nd:YAG laser
did not cause ulceration but did show a greater degree of thermal damage to the
lamina propria. Combined Nd:YAG/CO2 applications resulted in separation of the
perimysial fibers from the muscle fibers of the vocalis muscle. CONCLUSION:
These findings suggest that the noncontact Nd:YAG laser can be applied in a
controlled fashion to the canine larynx at appropriate power densities.
Anatomical differences between human and canine larynges are considered.
Extrapolation to humans is proposed.

Unique Identifier: 98409122

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HNO 1998 Jul;46(7):672-7

[Argon plasma surgery (APC) in the upper aerodigestive tract. Initial results].

[Article in German]

Bergler W, Farin G, Fischer K, Hormann K

Universitats-HNO-Klinik Mannheim.

Cold knife surgery, electrosurgery and laser surgery all offer techniques,
instruments, equipment and systems for resecting and destroying mucosal lesions
and for hemostasis in the upper aerodigestive tract. When used in the head and
neck, argon plasma surgery (APS) offers a new, contact-free, electrosurgical
technique in which high frequency current is applied through ionized, and thus
electrically conductive, argon(argon plasma) to the tissue undergoing
treatment. Especially noteworthy in APS are its advantages for removing a
lesion and controlling bleeding: the technique is easy to control, and the
depth of the thermal tissue destruction is limited to a maximum of 3 mm even in
wide-area application, so that damage to adjacent or submucosal tissues can be
avoided. Initial results with APS in the reduction of hyperplastic nasal
turbinates, treatment of hereditary hemorrhagic teleangiectasia (Osler's
disease) in the nasal mucosa, and in treating progressive juvenile
papillomatosis of the larynx have shown clear advantages for APS over other
methods used.

Unique Identifier: 98408149

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J Dermatol 1998 Jul;25(7):429-33

Management of female genital warts with an analog of imiquimod 2% in cream: a randomized, double-blind, placebo-controlled study.

Syed TA, Ahmadpour OA, Ahmad SA, Ahmad SH

Department of Dermatology University of California San Francisco 94143-0989,

USA.

The purpose of this randomized, double-blind, placebo-controlled study was to
determine the clinical efficacy and tolerability of an analog of imiquimod
(2%)in cream to cure genital warts in women. Sixty preselected women, ranging
between 18 and 45 years of age (mean 24.3) and having 411 lesions (mean 6.8)
with clinical, histopathological and polymerase chain reaction (PCR) confirmed
diagnosis of human papilloma virus (HPV) infection were randomized to two
parallel groups. Each patient received a precoded 40-g tube and instructions on
how to apply the trial medication to their lesions at home two times daily for
five consecutive days per week. The active treatment period was six weeks.
Patients were evaluated on a weekly basis. A clinically and PCR established
total clearance of target warts was recorded as a cure. By the end of the
treatment, 43.3% of patients and 42.8% of warts were cured. Code disclosure
revealed that imiquimod cream had cured 83.3% of the treated patients and 84.3%
of the tested warts, while the placebo healed one subject and four warts (p <
0.0001). Eight patients (13.3%) in the imiquimod group experienced mild to
moderate, non-objective, drug-induced symptoms with no dropouts. Among the 26
cured patients, five had a relapse after 11 months. In conclusion, the data
presented demonstrate that 2% imiquimod in cream with mild to moderate
subjective side effects is significantly more effective than placebo in
eliminating genital warts in women.

Unique Identifier: 98380706

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Anal Cell Pathol 1998;16(3):125-30

Detection of human papillomavirus type 2 related sequence in oral papilloma.

Yamaguchi T, Shindoh M, Amemiya A, Inoue N, Kawamura M, Sakaoka H, Inoue M,

Fujinaga K

Department of Preventive Dentistry, Kagoshima University Dental School,

Sakuragaoka, Japan.

Oral papilloma is a benign tumourous lesion. Part of this lesion is associated
with human papillomavirus (HPV) infection. We analysed the genetical and
histopathological evidence for HPV type 2 infection in three oral papillomas.
Southern blot hybridization showed HPV 2a sequence in one lesion. Cells of the
positive specimen appeared to contain high copy numbers of the viral DNA in an
episomal state. In situ staining demonstrated virus capsid antigen in
koilocytotic cells and surrounding cells in the hyperplastic epithelial layer.
Two other specimens contained no HPV sequences by labeled probe of full length
linear HPVs 2a, 6b, 11, 16, 18, 31 and 33 DNA under low stringency
hybridization conditions. These results showed the possibility that HPV 2 plays
a role in oral papilloma.

Unique Identifier: 98363521

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Am J Otolaryngol 1998 Jul-Aug;19(4):237-9

Estrogen and progesterone receptor expression in inverted papilloma.

Lapco PE, Barnes EL

Department of Otolaryngology, University of Pittsburgh School of Medicine, PA

15213, USA.

[ No abstract available]

Unique Identifier: 98355380

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Cancer Res 1998 Jul 15;58(14):3087-93

Cryptic open reading frames in plasmid vector backbone sequences can provide highly immunogenic cytotoxic T-lymphocyte epitopes.

van Hall T, van de Rhee NE, Schoenberger SP, Vierboom MP, Verreck FA, Melief

CJ, Offringa R

Department of Immunohematology and Blood Bank, Leiden University Medical

Center, The Netherlands.

Murine tumor cells obtained through transfection of expression plasmids
carrying activated cellular and/or viral oncogenes constitute formidable tools
for immunological tumor research. As reported previously, mouse embryo cells of
C57BL/6 origin, transformed by mutated p53 or human papilloma virus type 16
(HPV16), present, at their surface, MHC-bound peptides that are derived from
the p53 and the HPV16 E7 oncoproteins, respectively, which can serve as a
target for a highly effective antitumor T-cell response. Here, we describe the
identification, through molecular cloning, of an additional, highly
immunodominant peptide that is presented by the aforementioned HPV16- and
p53-transformed cells. This peptide is encoded by a cryptic open reading frame
in the backbone sequences of the plasmids that had been used to generate these
cells. Considerable amounts of transcripts encompassing this open reading frame
were detected in the cells concerned. These transcripts were the result of the
bidirectional nature of the retroviral long terminal repeat (LTR) present in
the expression plasmids used for transfection, which resulted in transcription
of the gene of interest, as well as in transcription of the vector sequences
positioned at the other side of the LTR. Due to this mechanism, all tumor cells
harboring LTR-driven expression plasmids expressed the highly immunogenic
peptide, whereas cells containing plasmids driven by more unidirectional
promoters exhibited lower levels of this peptide. LTR-driven expression
plasmids were also shown to encode this peptide epitope when used for DNA
vaccination, as mice vaccinated with such a plasmid developed a CTL response
against this peptide. Our data show that awareness of plasmid backbone-derived
epitopes is of crucial importance for the correct interpretation of preclinical
experiments and for the design of DNA vaccines.
Unique Identifier: 98343569
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Paediatr Anaesth 1998;8(4):357-61
 
 
Juvenile laryngeal papillomatosis: scary anaesthetic!
Theroux MC, Grodecki V, Reilly JS, Kettrick RG
Department of Anesthesia and Critical Care, duPont Hospital for Children,
Wilmington, DE 19899, USA.
We describe three children ages 20 to 33 months who presented for surgical
resection of their laryngeal papillomata. Their anaesthetic management revealed
the severity of obstruction which these children presented and the obstacles
that faced the anaesthesiologist trying to secure the airway and provide
adequate ventilation. The airway obstruction had both a fixed and a dynamic
component to it. This was evidenced by the ability of the children to maintain
ventilation when spontaneously breathing. But, they exhibited total obstruction
when ventilation was attempted via mask using positive pressure. It is possible
to encounter obstruction to ventilation after the trachea has been intubated
because of papillomata that were 'shaved off,' filling the tracheal tube lumen.

Unique Identifier: 98336809

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Laryngoscope 1998 Jul;108(7):968-72

A 585-nanometer pulsed dye laser treatment of laryngeal papillomas: preliminary report.

McMillan K, Shapshay SM, McGilligan JA, Wang Z, Rebeiz EE

Otolaryngology Research Center, Department of Otolaryngology, New England

Medical Center, Boston, Massachusetts 02111, USA. kathleen.mcmillan@es.nemc.org

OBJECTIVES/HYPOTHESIS: Standard management of recurrent respiratory
papillomatosis (RRP) currently consists of CO2 laser microsurgical ablation of
papillomas. Because of the recurrent nature of this viral disease, patients are
often faced with significant cumulative risk of soft tissue complications. As a
minimally traumatic alternative to management of RRP, we have investigated the
use of the 585-nm pulsed dye laser (PDL) to cause regression of papillomas by
selective eradication of the tumor microvasculature. STUDY DESIGN:
Nonrandomized prospective pilot study. METHODS: Patients with laryngeal
papillomas were treated with the PDL at fluences of 6 J/cm2 (double pulses per
irradiated site), 8 J/cm2 (single pulses), and 10 J/cm2 (single pulses), at
noncritical areas within the larynx, using a specially designed
micromanipulator. Lesions on the true cords were treated with the CO2 laser,
using standard methodology. RESULTS: Clinical examination of three patients
treated to date showed that PDL treatment appeared to produce complete
regression of papillomas. Unlike the sites of lesions treated by the CO2 laser,
the epithelial surface at the PDL treatment sites was preserved intact.
CONCLUSIONS: These preliminary results suggest the PDL may eradicate
respiratory papillomas with minimal damage to normal laryngeal tissue. Further
analysis of the ongoing study is required to demonstrate potential benefits of
the technique.

Unique Identifier: 98328177

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Laryngoscope 1998 Jul;108(7):962-7

Efficacy of DHE photodynamic therapy for respiratory papillomatosis: immediate and long-term results.

Shikowitz MJ, Abramson AL, Freeman K, Steinberg BM, Nouri M

Department of Otolaryngology and Communicative Disorders, Long Island Jewish

Medical Center, The Long Island Campus for the Albert Einstein College of

Medicine, New Hyde Park, New York 11040, USA.

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis is a potentially
life-threatening disease that affects both children and adults and can result
in complete respiratory obstruction. Conventional therapies cannot prevent
multiple recurrences. The authors have been evaluating photodynamic therapy
(PDT) to treat this disease since 1988. This study compared the efficacy of PDT
with dihematoporphyrinether (DHE) with traditional therapy. STUDY DESIGN: This
was a randomized prospective trial of DHE-PDT. Patients were randomly assigned
to receive one of two doses of DHE--3.25 mg/kg or 4.25 mg/kg body weight. They
were compared with a concurrent control group. Disease extent was evaluated by
direct laryngoscopy before treatment and over a 1-year period following
treatment. Results were also compared with two historical cohorts of patients
treated with lower doses of DHE. METHODS: Eighty-one patients, ages 4 to 74
years, with moderate to severe recurrent disease were enrolled. Forty-eight
received PDT and 33 in the control group were treated with conventional
therapy. Both PDT groups received 50 J laser light to activate the drug.
Patients received an intravenous infusion of DHE as outpatients 48 to 72 hours
before treatment. During direct laryngoscopy, light (630 nm) was delivered by
an argon-pumped dye laser. Tissue biopsies were analyzed for presence of human
papillomavirus (HPV). RESULTS: There was notable improvement with either drug
dose over the first year. Those receiving 4.25 mg/kg DHE experienced a
significantly larger decrease in papilloma growth rate. Three-year follow-up of
a subset of patients confirmed that improvement was maintained. There was no
impact of DHE-PDT on persistence of HPV DNA. CONCLUSION: This therapy holds
promise for the treatment of laryngeal papillomas.

Unique Identifier: 98328176

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Head Neck 1998 Aug;20(5):418-24

Recurrent respiratory papillomatosis.

Derkay CS, Rimell FL, Thompson JW

Children's Hospital of King's Daughter, Norfolk, Virginia, USA.

[No abstract available]

Unique Identifier: 98326803

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Virus Res 1998 Mar;54(1):23-9

Synthetic peptides of human papillomavirus type 18 E6 harboring HLA-A2.1 motif can induce peptide-specific cytotoxic T-cells from peripheral blood mononuclear cells of healthy donors.

Yoon H, Chung MK, Min SS, Lee HG, Yoo WD, Chung KT, Jung NP, Park SN

Virus/Oncology Research Unit, Korea Research Institute of Bioscience and

Biotechnology, KIST, Yusong, Taejon, South Korea.

To identify cytotoxic T-cell (CTL) epitopes against human papillomavirus type
18 (HPV 18) E6 protein that might be useful for developing peptide-based
vaccine against HPV 18 infection, 18 peptides which possibly contain CTL
epitopes were selected on the basis of previously described human leukocyte
antigen (HLA)-A2.1-binding motif and chemically synthesized. In the binding
assay of the synthetic peptides, 8 out of 18 synthetic peptides enhanced the
expression of HLA-A2.1 molecules on T2 cell surface, which implies that these
peptides were able to bind the HLA molecules. Those peptides having good
binding affinity to HLA-A2.1 were tested for their ability to activate CTLs
which were isolated from peripheral blood mononuclear cells (PBMCs) of healthy
blood donors and to kill the target T2 cells pulsed with the same peptide. Five
out of eight tested peptides activated CTLs and killed the target cells.

Unique Identifier: 98321505

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Laryngoscope 1998 Jun;108(6):935-7

A staging system for assessing severity of disease and response to therapy in recurrent respiratory papillomatosis.

Derkay CS, Malis DJ, Zalzal G, Wiatrak BJ, Kashima HK, Coltrera MD

Department of Otolaryngology Head-Neck Surgery, Eastern Virginia Medical

School, Norfolk 23507, USA.

Recurrent respiratory papillomatosis (RRP) is perplexing and frustrating disease for both the families it afflicts and the physicians who care for them. Although RRP is a benign disease of viral etiology (most commonly HPV types 6 and 11), it has potentially morbid consequences owing to its involvement of the airway and the risk of malignant conversion. Treatment of RRP has been mainly surgical over the past half century, relying on operative debulking, although adjuvant medical therapies have been utilized for recalcitrant cases. Among the most frustrating aspects of this disease is the observation that whereas some patients demonstrate limited disease with an infrequent need for intervention, others are confronted with recurrent airway compromise and a repeated need for laser surgery.

Although it is considered the most common benign neoplasm of the larynx, RRP is an orphan disease with an incidence in the United States estimated at between 1500 and 2500 new cases per year. Owing to the relative paucity of cases and the complicated nature of their treatment, the majority of children with RRP are cared for in universities, major medical centers, and children's hospitals.

Although several scoring and staging systems have been proposed, clinicians and researchers have not yet adopted a uniformly acceptable nomenclature for describing RRP lesions that is simple yet comprehensive. This has created confusion in the RRP literature and in physician-to-physician communications regarding patient's response to therapies. In addition, the absence of a universally accepted staging system has hampered our abilities to accurately report the results of adjuvant therapies or document the natural course of the disease.

In conjunction with the Centers for Disease Control and Prevention-sponsored Multi-Institutional Task Force on RRP, the Collaborative Anti-Viral Study Group HPV Subcommittee, and the authors of the most widely used current severity scales, we propose a new severity/staging system for RRP. This format incorporates the best qualities of the existing systems by numerically grading the extent of papillomatosis at defined aerodigestive subsites, assesses functional parameters, diagramatically catalogs subsite involvement, and assigns a final numeric score tot he patient's current extent of disease. Utilizing software designed at the University of Washington (Seattle, WA) and licensed to the American Society of Pediatric Otolaryngology, this staging system is now computerized and available to pediatric otolaryngologists and bronchoesophagologists to allow them to objectively and subjectively measure an individual patient's clinical course and response to therapy over time.

Unique Identifier: 98290477

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Laryngorhinootologie 1998 Mar;77(3):157-64

[Clinical and molecular biology studies of respiratory papillomatosis].

[Article in German]

Mahnke CG, Werner JA, Frohlich O, Lippert BM, Hoffmann M, Rudert HH

Klinik fur Hals-, Nasen- und Ohrenheilkunde, Kopf- und Halschirurgie,

Christian-Albrechts-Universitat Kiel.

BACKGROUND: Recurrent laryngeal papillomatosis is a benign neoplastic disease
which is probably caused by but at least associated with the human
papillomavirus. It can be of significant importance for the affected patients
because of its recurrent clinical course. A great variety of therapeutic
measures has been described including the surgical removal either with
conventional instruments or using the laser. Development of malignancies from
papillomas have been reported. PATIENTS: The clinical courses of all 95
patients who have been treated for laryngeal papillomatosis since 1960 were
analysed retrospectively. The two most common forms of treatment, surgical
removal either conventionally or with the use of the laser, were compared. "Hot
start" polymerase chain reaction and Southern blot hybridization were used to
detect HPV DNA. The case reports of all patients developing cancer of the
larynx are included. RESULTS: Laryngeal papillomatosis is a disease of all
ages, more often first diagnosed in the first and fourth decade. Puberty had no
effect on the clinical course. The different forms of treatment did not affect
the rate of recurrence. However, the rate of complications such as tracheostomy
and glottic webs was significantly reduced after laser surgery. Since the
introduction of this new form of therapy no more tracheostomies had to be
performed on these patients. HPV DNA was found in four of five samples (HPV
6:3, HPV 11:1). Squamous cell carcinoma subsequently developed in four cases,
three of which occurred almost simultaneously and were therefore not included.
CONCLUSION: The term juvenile laryngeal papillomatosis should be replaced by
recurrent respiratory papillomatosis. One could then distinguish according to
the age of onset, i.e., in children below the age of 16 years and in
adolescents and adults older than 15 years. The occurrence of squamous cell
carcinomas in patients previously treated for papillomas underlines the need
for repeated histological studies. The surgical treatment remains the mainstay
in the management of laryngeal papillomatosis. The laser surgical technique is
superior to conventional removal. Using the at present most sensitive and
specific methods HPV DNA can be detected in a large percentage of laryngeal
papillomas.

Unique Identifier: 98238795

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Vaccine 1998 Apr;16(6):613-23

Intracutaneous vaccination of rabbits with the E6 gene of cottontail rabbit papillomavirus provides partial protection against virus challenge.

Sundaram P, Tigelaar RE, Xiao W, Brandsma JL

Section of Comparative Medicine, Yale University School of Medicine, New Haven,

CT 06520, USA.

DNA vaccination of rabbit skin with the L1 gene of cottontail rabbit
papillomavirus (CRPV) has previously been shown to induce prophylactic immunity
against CRPV. We now describe the effects of vaccination with the CRPV E6 gene,
using the same approach. The experimental vaccine pdCMV-E6 encoded both the
truncated and full length forms of CRPV E6 protein. The control vaccine
pCMV-beta encoded beta galactosidase. Rabbits were vaccinated with DNA-coated
gold particles, using a gene gun. Each rabbit received an initial vaccination
with 30 micrograms DNA and 3 weeks later a booster vaccination, also with 30
micrograms DNA. pdCMV-E6-vaccinated rabbits developed E6-specific cellular
immunity as determined by proliferation assays using peripheral blood
mononuclear cells from animals prior to challenge, but did not develop
detectable humoral immunity to E6 proteins, as evaluated by ELISA using two
different E6 antigen preparations. Control rabbits developed humoral immunity
to beta galactosidase. All rabbits were challenged by infection of nine skin
sites with live CRPV virus and monitored for papilloma formation. None of four
control rabbits was protected at any of the challenge sites. Of six rabbits
vaccinated with pdCMV-E6, two were completely protected and one was virtually
completely protected (tiny papillomas at just two of nine challenge sites).
These three rabbits also exhibited significant E6-specific in vitro
proliferative responses. The four E6 DNA-vaccinated rabbits that were not
completely protected exhibited evidence of partial protection: some challenge
sites did not form papillomas; papilloma onset was delayed; papilloma burden
was less. These results demonstrate that partial prophylaxis against
papillomavirus-induced disease can be achieved by intracutaneous vaccination
with a recombinant plasmid encoding the papillomavirus.

Unique Identifier: 98230929

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Pediatr Surg Int 1998 Apr;13(4):301-3

Papillomavirus-induced genital warts in a girl--management by surgery and immunomodulating therapy.

Trobs R, Metzner G, Friedrich T, Pustowoit B, Handrick W, Nestler I

Universitat Leipzig, Klinik fur Kinderchirurgie, Leipzig, Germany.

A 4-year-old girl with condylomata acuminata of the vulva and papular warts of
the surrounding skin is presented. The lesions were removed by surgery.
Histologic investigation showed koilocytosis of the squamous epithelium and
in-situ hybridization revealed human papilloma virus type 6 infection. There
were no signs of sexual abuse or sexual transmission of the virus. After
ablation, an interferon-containing ointment was applied. In order to prevent
recurrence, a low-molecular-weight immunomodulating leucocyte fraction was
given for more than 1 year, during which time no relapse was observed.

Unique Identifier: 98221264

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RRP Foundation
P.O. Box 6643

Lawrenceville NJ 08648-0643