Summer 1998

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Volume 5 • 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 (generally 1996 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: rrpf@aol.com or wfs@gfdl.gov

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

Otolaryngol Head Neck Surg 1998 Jun;118(6):810-815

Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis.

Rosen CA, Woodson GE, Thompson JW, Hengesteg AP, Bradlow, HL

Department of Otolaryngology--Head and Neck Surgery, University of

Pittsburgh Medical Center, Pennsylvania, USA.

OBJECTIVE: We report the
preliminary results of a phase I trial using indole-3-carbinol for the
treatment of recurrent respiratory papillomatosis. Indole-3-carbinol is
a chemical that is found in high concentrations in cruciferous
vegetables and has been shown to alter the growth pattern of recurrent
respiratory papillomatosis cell cultures and to be effective in an in
vivo animal model of recurrent respiratory papillomatosis. METHODS:
Eighteen patients were treated with oral indole-3-carbinol and had a
minimum follow-up of 8 months and a mean follow-up of 14.6 months. All
patients received indole-3-carbinol, and outcome measures included a
change in papilloma growth rate and the need for surgery during
treatment compared with before treatment. All patients had serial
examinations with videoendoscopy to document papilloma location and
growth rate. RESULTS: Thirty-three percent (6 of 18) of the study
patients had a cessation of their papilloma growth and have not required
surgery since the start of the study. Six patients have had reduced
papilloma growth rate, and 6 (33%) patients have shown no clinical
response to indole-3-carbinol. Indole-3-carbinol affects the ratio of
hydroxylation of estradiol; changes in the ratios of urinary
2-hydroxylation and 16-hydroxylation of estradiol caused by
indole-3-carbinol correlated well with clinical response. No major
complications or changes in the children's growth curve were noted.
CONCLUSIONS: The preliminary results of treating recurrent respiratory
papillomatosis with indole-3-carbinol holds promise. Longer follow-up of
this patient group and a blinded, controlled trial are required. We
conclude that indole-3-carbinol appears to be safe and well tolerated
and may be an efficacious treatment for recurrent respiratory
papillomatosis.

Unique Identifier: 98288931

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Arch Otolaryngol Head Neck Surg 1998 May;124(5):541-544

S-phase fraction as a predictor of prognosis in juvenile respiratory papillomatosis.

Stern Y, Mueller K, Willging JP, Myer CM 3rd, Cotton RT

Department of Pediatric Otolaryngology and Maxillofacial Surgery, Children's

Hospital Medical Center, University of Cincinnati College of Medicine, Ohio 45229, USA.

OBJECTIVE: To determine whether DNA ploidy and the S-phase fraction are
predictive of the clinical course in children with recurrent respiratory
papillomatosis. DESIGN: Masked compression of DNA analysis findings to the
clinical course of the disease. SETTING: Tertiary referral center. PATIENTS:
All pediatric patients treated for recurrent respiratory papillomatosis at our
institution between 1989 and 1995 who had adequate follow-up and whose primary
biopsy specimen was available for examination. Fifty-five patients met these
criteria. METHODS: Information was collected from the case notes on the
patient's age at presentation, sex, sites of disease, duration of active
disease, and frequency of operative interventions. Flow cytometric analysis was
performed on the archival paraffin-embedded primary biopsy specimen obtained at
the initial surgical excision, providing DNA content and percentages of S-phase
cells. The investigators who performed the DNA analysis were masked to the
clinical course. RESULTS: The age of the patients at presentation ranged from 3
months to 16 years. Thirty patients had involvement in more than 1 anatomical
site. The disease in 10 patients had spread to the distal tracheobronchial
tree. The patients underwent a total of 1124 procedures, with a frequency range
of 7 to 27 per year. All cell populations studied were diploid. The percentage
of S-phase cells was significantly higher in the primary biopsy specimen from
patients with disease characterized by more frequent recurrences, multiple sites,
and distal extension (P<.05). In multiple regression analysis, the
S-phase fraction was found to be an independent and powerful prognostic factor
for aggressive disease. CONCLUSIONS: The S-phase fraction may be predictive of
the clinical course in patients with juvenile respiratory papillomatosis.
Prospective studies are needed to assess the diagnostic and clinical value of
our primary results and to determine whether DNA analysis can assist in
identifying patients at increased risk for an aggressive clinical course.

Unique Identifier: 98266016

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Laryngoscope 1998 May;108(5):735-740

Malignant transformation of recurrent respiratory papillomatosis associated

with integrated human papillomavirus type 11 DNA and mutation of p53.

Rady PL, Schnadig VJ, Weiss RL, Hughes TK, Tyring SK

Department of Microbiology and Immunology, University of Texas Medical Branch,

Galveston 77555-1019, USA.

Recurrent respiratory papillomatosis (RRP), usually confined to the
nasopharynx, trachea, and larynx, occasionally can progress to extensive
bronchopulmonary disease. Most cases of bronchopulmonary and laryngeal
papillomatosis are cytologically benign and do not undergo malignant
transformation; however, squamous cell carcinoma (SCC) can arise in RRP in the
absence of known risk factors such as radiation and smoking. In this study, the
authors investigated molecular genetic alterations occurring in a case of
metastasizing SCC that arose in long-standing bronchopulmonary papillomatosis.
Genomic DNA from tracheal papillomata, tracheobronchial papillomata, SCC of the
lung, and a lymph node metastasis was extracted. The physical state of the
human papillomavirus type 11 (HPV-11) DNA was investigated by two-dimensional
gel electrophoresis. Molecular genetic alterations of the host genome were
studied by direct sequencing of polymerase chain reaction-amplified gene
fragments and restriction fragment length polymorphism (RFLP) analysis.
Episomal and integrated forms of HPV-11 sequences were detected in
histologically benign tumors, but only the integrated form of the viral DNA
could be found in malignant tissue samples. Molecular genetic studies revealed
that an allelic loss of the interferon-beta gene (IFNbeta-1) and an endogenous
type of mutation of the p53 antioncogene were found only in the malignant
lesions. Mutations were not observed in the ras, neu, or multiple tumor
suppressor (MTS1/p16) genes in any specimens. The authors' data indicated that
the p53 genetic mutation was associated with integration of HPV-11 in
histologically malignant lesions. This association may promote a progressive
genetic instability that can lead to the development and clonal expansion of
malignant lesions in RRP.

Unique Identifier: 98252230

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Arch Pediatr Adolesc Med 1998 Apr;152(4):407-408

Pathological case of the month. Recurrent respiratory papillomatosis.

Ray R, Debich-Spicer D, Borrego O, Gilbert-Barness E

Department of Pediatrics, University of South Florida, Tampa, USA.

[No abstract available]

Unique Identifier: 98218624

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Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1998 Mar;168(3):299-301

[Pulmonary manifestation of juvenile laryngotracheal papillomatosis].

[Article in German]

Conrad R, Baselides P, Kandyba J, Layer G, Schild HH

Radiologische Universitatsklinik Bonn.

[No abstract available]

Unique Identifier: 98212478

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Cancer Res 1998 Apr 1;58(7):1435-1443

Topical retinoic acid reduces skin papilloma formation but resistant papillomas

are at high risk for malignant conversion.

Tennenbaum T, Lowry D, Darwiche N, Morgan DL, Gartsbein M, Hansen L, De Luca LM, Hennings H, Yuspa SH

Department of Life Sciences, Bar Ilan University, Ramat-Gan, Israel.
Retinoic acid (RA) was topically applied to the skin of Sencar mice during the
promotion phase of specific tumor induction protocols that produce papillomas
at low (12-O-tetradecanoylphorbol-13-acetate promoted, TPA) or high
(mezerein-promoted) risk for premalignant progression and malignant conversion.
RA consistently reduced the yield of papillomas and carcinomas in both
protocols, but the frequency of malignant conversion in papillomas that emerged
during RA treatment was not reduced. When TPA was reapplied after cessation of
RA treatment, the number of papillomas increased 2-fold, suggesting that RA had
not eliminated initiated cells. In vitro, RA prevented the emergence of
transformed keratinocytes in an assay that mimics malignant conversion,
suggesting that RA can suppress conversion if applied during the stage of
premalignant progression. Examination of tumor markers at weeks 14 and 22 of
the tumor-induction experiments in vivo indicated that papillomas evolving
during RA treatment exhibited a phenotype of high progression risk, even in the
TPA-promoted groups. In the majority of these tumors, the alpha6beta4 integrin
and retinoid X receptor alpha transcripts were detected suprabasally,
indicating an advanced state of premalignant progression. RA-treated tumors
also expressed higher levels of transcripts for transforming growth factor
(TGF)-beta1 and localized TGF-beta1 peptide in the basal portions of the tumor
fronds. Because up-regulated expression of TGF-beta1 suppresses papilloma
formation, these studies suggest a mechanism whereby RA can prevent papilloma
eruption via a TGF-beta intermediate, but papillomas resistant to RA may have
altered TGF-beta signaling and progress to carcinomas at an increased
frequency.

Unique Identifier: 98196535

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Genitourin Med 1997 Oct;73(5):387-390

Type 1 cytokine response and treatment outcome of genital HPV lesions.

Stellato G, Nieminen P, Aho M, Lehtinen T, Lehtinen M, Paavonen J

Department of Obstetrics and Gynecology, University Hospital, Helsinki, Finland.

OBJECTIVES: To determine the role of type 1 cytokines as predictors of response
to treatment of genital HPV lesions with laser ablation with or without
adjuvant systemic interferon alpha 2b (IFN-alpha). METHODS: Measurement of
serum interleukin 2 (IL-2), IL-2 soluble receptor alpha (sIL-2 alpha),
interferon gamma, and human papilloma virus (HPV) DNA in patients undergoing
treatment of genital HPV lesions with carbon dioxide laser and systemic
IFN-alpha. A randomised, placebo controlled study of 92 cases with 6 months of
follow up. RESULTS: High IL-2/sIL-2 alpha was associated with 60% to 70%
protection against recurrences both in the IFN-alpha and placebo groups (OR =
0.4, 90%, CI 0.1-2.5; OR = 0.3, 90% CI 0.0-1.8, respectively). Diagnostic phase
serum IL-2 predicted favourable outcome (OR = 0.2, 90% CI 0.0-1.0) in women
with high load of HPV DNA or HPV 16/18 DNA regardless of the adjuvant therapy.
CONCLUSIONS: Serum IL-2 determinations may identify women with good prognosis
following laser ablation of genital HPV lesions.

Unique Identifier: 98196249

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Allergy Asthma Proc 1998 Jan;19(1):11-13

Laryngeal papilloma presenting as steroid-dependent asthma in a 3-year-old child without recurrent stridor.

Wilson NW, Millman E, Hogan MB

Department of Pediatrics, West Virginia University School of Medicine, Morgantown 26506-9214, USA.

Upper airway obstruction is well described as a cause of apparent asthma. However, it can be
very difficult to diagnose in young children. This 3-year-old male presented with a 1-year
history of severe recurrent wheezing with six emergency room visits in the previous 5 months.
Cromolyn, inhaled corticosteroids, and frequent predinisolone bursts had not controlled the
wheezing. There was no history of barky cough, croup, or stridor. His physical examination was
notable for marked nasal obstruction. At initial presentation, his lungs were normal with no
wheezing or stridor. Soft tissue neck X-ray films suggested the presence of a subglottic mass. A
large solitary papilloma was found on bronchoscopy. After surgical removal, there was no
further wheezing noted by either the parents or his physicians. Laryngeal papillomatosis may
mimic asthma in the absence of symptoms of hoarseness, croup, or stridor. It should be
particularly considered in 2 to 4-year-old children with recurrent wheezing that is poorly
responsive to aggressive therapy including oral corticosteroids.

Unique Identifier: 98193487

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J Ethnopharmacol 1998 Feb;60(1):71-78

Cancer chemopreventive and therapeutic activities of red ginseng.

Xiaoguang C, Hongyan L, Xiaohong L, Zhaodi F, Yan L, Lihua T, Rui H

Department of Pharmacology, Institute of Materia Medica, Chinese Academy of

Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.

Red ginseng extract A and B are the active components of Panax ginseng. Red
ginseng is a classical traditional Chinese medicine. Among Chinese herbs, red
ginseng has been considered as one of the tonics. Many studies indicated that
red ginseng could enhance immune function of the human body. The effects of red
ginseng extracts on transplantable tumors, proliferation of lymphocyte,
two-stage model and rat liver lipid peroxidation were studied. In a two-stage
model, red ginseng extracts had a significant cancer chemoprevention. At 50-400
mg/kg, they could inhibit DMBA/Croton oil-induced skin papilloma in mice,
decrease the incidence of papilloma, prolong the latent period of tumor
occurrence and reduce tumor number per mouse in a dose-dependent manner. Red
ginseng extract B could effectively inhibit the Fe2+/cysteine-induced lipid
peroxidation of rat liver microsome, suggesting that red ginseng extract B has
a stronger antioxidative effect than that of extract A. The results indicated
that red ginseng extracts (50 approximately 400 mg/kg) could significantly
inhibit the growth of transplantable mouse sarcoma S180 and melanoma B16. Red
ginseng extracts A (0.5 mg/ml) and B (0.1 and 0.25 mg/ml) might effectively
promote the transformation of T lymphocyte, but there was no influence on
lymphocyte proliferation stimulated by concanavalin A. This suggests that red
ginseng extracts have potent tumor therapeutic activity and improve the cell
immune system.

Unique Identifier: 98192104

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Arch Otolaryngol Head Neck Surg 1998 Mar;124(3):281-287

Iatrogenic airway stenosis with recurrent respiratory papillomatosis.

Perkins JA, Inglis AF Jr, Richardson MA

Otolaryngology-Head and Neck Service, Madigan Army Medical Center, Tacoma, Wash, USA.

OBJECTIVE: To describe the presentation of, factors contributing to, and
treatment of iatrogenic airway stenosis (IAS) associated with recurrent
respiratory papillomatosis (RRP). DESIGN: Retrospective case series. SETTING:
Pediatric tertiary care center. PATIENTS: The charts of patients treated for
RRP in our institution from 1980 to 1995 (N=50) were reviewed. Seven patients
were identified as having IAS based on endoscopic findings. MAIN OUTCOME
MEASURES: Prevalence and types of IAS within our RRP patient population,
methods used to treat IAS, and successful treatment of IAS. RESULTS: Of the 7
patients identified, 3 had isolated posterior glottic stenosis (PGS) and 1 had
isolated subglottic stenosis. The other 3 had multiple areas of IAS as follows:
PGS with bronchial stenosis, supraglottic stenosis with PGS, and tracheomalacia
with tracheal stenosis from a suprastomal granuloma. The factors associated
with IAS were extensive papilloma growth in the posterior glottis, prolonged
periods of frequent laryngoscopies, and the use of nonstandard therapies, which
in our series included topical podophyllum resin or photodynamic therapy. Six
patients, all of whom had tracheal RRP at some point in their disease process,
required tracheotomy. Five patients required laryngotracheal reconstruction.
Laryngotracheal reconstruction permitted decannulation in all cases. Tracheal
papillomas became sessile and nonobstructive after decannulation.
Laryngotracheal reconstruction with rib grafting was most frequently performed.
Of our 50 patients, none who did not have IAS required a tracheotomy. Of the 44
patients who did not require a tracheotomy, only 1 had tracheal papillomas.
CONCLUSIONS: Occasionally, therapy for RRP is complicated by IAS. In our
series, PGS was most common. Tracheotomy was associated with the presence of
both IAS and distal RRP. In selected cases, laryngotracheal reconstruction can
be successfully accomplished when RRP is present, and subsequent regression of
tracheal RRP is likely.

Unique Identifier: 98184424

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Laryngorhinootologie 1998 Jan;77(1):27-33

[Clinical and molecular biology studies of laryngeal papillomatosis]. [Article in German]

Mahnke CG, Werner JA, Frohlich O, Lippert BM, Hoffman H, 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 Papilloma Virus. It can be of
significant importance for the affected patients because of its recurrent clinical course. A wide
variety of therapeutic measures have been described including the surgical removal either with
conventional instruments or laser. Malignancies developing 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 before
age 10 or after age 30. Puberty had no effect on the clinical course. However, the rate of
complications such as tracheostomy and glottic webs was significantly reduced after laser
surgery. HPV-DNA was found in 10 of 11 samples. 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. 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 most sensitive and
specific methods presently available, HPV-DNA can be detected in a large percentage of
laryngeal papillomas.

Unique Identifier: 98182778

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J Med Virol 1998 Mar; 54(3):219-225

Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine].

Snoeck R, Wellens W, Desloovere C, Van Ranst M, Naesens L, De Clercq E, Feenstra L

Rega Institute for Medical Research, K.U.Leuven, Belgium.

Respiratory papillomatosis is a rare and often severe disease, usually localized in
the larynx. It may cause respiratory distress and even life-threatening
obstruction of the airways. Treatment is generally based on the
evaporation of the lesions with a CO2 laser, but microsurgery, cytotoxic
and/or cytostatic drugs, interferons, and vaccines are also used.
Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] (HPMPC)
was shown to suppress the growth of tumors induced by rabbit
papillomavirus as well as human papillomavirus (HPV). The efficacy of
cidofovir was assessed in 17 patients with severe respiratory
papillomatosis. Cidofovir at a concentration of 2.5 mg/ml was injected
directly in the different laryngeal papillomatous lesions during
microlaryngoscopy under general anesthesia. Biopsies were taken before
the treatment was started both for anatomopathology and viral typing.
HPMPC kinetics in serum was monitored in three patients, the drug levels
being determined by high-performance liquid chromatography. Complete
disappearance of the papillomatosis was observed in 14 patients. Four
patients relapsed and were successfully treated again with cidofovir. Of
the three remaining patients, one progressed while under treatment with
cidofovir, after an initial marked response. One patient had a partial
remission and remained stable for more than 1 year after the last
injection. He had a very aggressive and extensive disease originally.
Finally, one patient was lost to follow-up after four injections.
Intratumoral injections of cidofovir for the treatment of severe
laryngeal papillomatosis is a powerful new therapeutic approach for this
disease. Treatment was well tolerated, and no significant side effects
were noted.

Unique Identifier: 98175525

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Minerva Stomatol 1997 Nov;46(11):595-601

[Role of human papilloma virus in precancerous and cancerous lesions of the

oral cavity. Review of the literature]. [Article in Italian]

Santoro V, Pozzuoli ML, Colella G

Istituto di Chirurgia Orale e Maxillo Facciale, Facolta di Medicina e Chirurgia, Seconda Universita degli Studi, Napoli.

The authors review the literature on the role of human papilloma virus in
premalignant and malignant oral tumours. They describe the biomolecular
mechanisms of action and report the data of other authors regarding the
incidence of the DNA of HPV in both normal mucosa of healthy subjects and in
patients affected by disease, in tissues taken from benign and malignant
lesions of the oral cavity. Having commented on these findings, they discuss
the possible interference of analysis techniques, various kits and clinical
conditions may have on the final results.

Unique Identifier: 98150613

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Clin Otolaryngol 1997 Aug; 22(4):375-376

The effect of microdebriders on tissue for histological diagnosis.

McGarry GW, Gana P, Adamson B

Department of Otolaryngology Head and Neck Surgery, Royal Infirmary, Glasgow, UK.

Microdebriders are an innovation in endonasal surgery which enable accurate and
precise removal of tissue without damaging the surrounding mucosa. Concern has
been expressed, however, that the instrument may render excised tissue
unsuitable for histological diagnosis. This problem is further compounded by
the fact that the Hummer (Stryker UK Ltd) microdebrider does not incorporate a
mechanism for collecting specimens at the time of removal. Twenty-one patients
with sinonasal polyposis underwent endoscopic sinus surgery using the
microdebrider. Specimens were collected at the time of surgery via an in-line
specimen trap. Simultaneous conventional biopsies of adjacent tissue were taken
for comparison. The tissue was fixed in formalin then routinely processed to
paraffin wax prior to staining with haematoxylin and eosin (H&E). A
histological diagnosis was made in all 21 patients. A single unsuspected
transitional cell papilloma was found. The remaining 20 specimens consisted of
inflammatory nasal polypi. In two non-caseating granulomas were identified.
Traumatic artefact was limited to the respiratory epithelium. The
sub-epithelial tissue was unaffected and metaplastic epithelium appeared
intact. The use of microdebriders does not preclude the submission of tissue
for histological analysis. Tissue obtained has limited artefact and is suitable
for pathological diagnosis.

Unique Identifier: 97443945

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Nurse Pract 1997 Apr;22(4):24-25

Human papillomatous virus infection update: impact on women's health.

Carson S

Columbia Wesley Women's Care Clinic, Wichita, Kan, USA.

Human papilloma virus (HPV) is one of the sexually transmitted diseases (STDs)
seen throughout the population. More than 60 types of HPV have been identified,
and 20 are known to cause genital warts; other types of HPV have an oncogenic
potential. During pregnancy, genital warts may grow (possibly due to a
suppressed immune system) and the neonate may become exposed. Several cofactors
that have been identified in the development of HPV include oral contraceptive
use, pregnancy and parity, nutrition, smoking, unsafe sex practices, and
immunosuppression. Treatment options are aimed at destroying the visible
lesions and include topical therapy, laser vaporization, cryocautery, liquid
nitrogen, or simple excision. Health care providers have an important role in
counseling about HPV infections. This includes educating clients about risk
factors, prevention, signs and symptoms of STDs including HPV, safe sex
practices, and the importance of regular examinations. Empowerment and a
positive approach must be taken to help the client understand that she has a
right to protect herself from STDs including HPV.

Comments:

Comment in: Nurse Pract 1997 Aug; 22(8):19, 22

Unique Identifier: 97274911

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J Clin Endocrinol Metab 1997 Apr; 82(4):1001-1006

Altered hydroxylation of estrogen in patients with postmenopausal osteopenia.

Lim SK, Won YJ, Lee JH, Kwon SH, Lee EJ, Kim KR, Lee HC, Huh KB, Chung BC

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

To study the possible contributions of the differences in estrogen
metabolism to bone mass in postmenopausal osteopenia, spinal and femoral
bone mineral densities (BMD) were measured, and 18 urinary metabolites
of estrogen were analyzed by a gas chromatography-mass spectrometry
assay system in 59 postmenopausal women (5-10 yr after menopause). The
BMD of the spine and femoral neck showed positive correlations with body
weight, height, and body mass index as we expected. Compared to
nonosteopenic subjects, there were no significant differences in serum
estrone (E1) and estradiol (E2) levels in patients with osteopenia.
However, the urinary 16 alpha-hydroxyestrone [16 alpha-(OH)E1] level was
significantly lower in patients with spinal osteopenia (P < 0.001).
Among the 18 urinary metabolites of estrogen, the 16 alpha-(OH)E1 and 16
alpha-(OH)E1/2-hydroxyestrone [2-(OH)E1) ratio showed positive
correlations with spinal BMD (P < 0.05), whereas 2-(OH)E2 showed a
negative correlation with femoral neck BMD (P < 0.05). The urinary 16
alpha-(OH)E1 level also revealed a positive correlation with the
age-matched z score of BMD in the spine (P < 0.05). In multiple stepwise
regression analysis, weight, 16 alpha-(OH)E1, interaction between 16
alpha-(OH)E1 and 2-(OH)E2, 2-(OH)E2, and years after menopause were
statistically significant for spinal BMD (r2 = 0.4968). For femoral neck
BMD and weight, 16 alpha-(OH)E1 and 2-(OH)E2 were the independent
determinants (r2 = 0.3369). In conclusion, the activity of estrogen 16
alpha-hydroxylase was decreased and/or the activity of estrogen
2-hydroxylase was enhanced in post-menopausal osteopenia. We speculated
that these derangements may serve as contributing factors for the
acceleration of bone loss in post-menopausal osteoporosis.

Unique Identifier: 97255217

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Toxicol Appl Pharmacol 1996 Nov;141(1):68-75

Effects of developmental exposure to indole-3-carbinol or 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproductive potential of male rat offspring.

Wilker C, Johnson L, Safe S

Department of Veterinary Anatomy and Public Health, Texas A&M University,

College Station 77843-4466, USA.

Treatment of pregnant female Sprague-Dawley rats on Gestational Day 15 with a
single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.5, 1.0, or
2.0 micrograms/kg) or indole-3-carbinol (I3C, 1.0 or 100 mg/kg), an aryl
hydrocarbon (Ah) receptor agonist which is found in cruciferous vegetables,
resulted in reproductive abnormalities in the male offspring (three to five
litters in each treatment group). Anogenital distance and crown to rump length
were altered by both compounds; however, the timing of the effects (Day 1 or 5)
was variable and the responses were not necessarily dose-dependent. In
62-day-old offspring, seminal vesicle (24 to 26%), prostate (32 to 44%),
testicular parenchymal (14%), and epididymal weight (19%) were decreased by one
or more doses of TCDD. In contrast, I3C at one or more doses decreased daily
sperm production/g testicular parenchyma (13 to 20%) and daily sperm
production/testis (22%). Total number of sperum in the epididymis was
significantly decreased (30 to 33%) in rats perinatally exposed to TCDD and
this was due to a decreased (49 to 51%) number of sperm in the tail of the
epididymis. Perinatal exposure to I3C did not affect any of these parameters.
TCDD did not affect epididymal transit time of sperm through the complete
epididymis at any of the doses (0.5 to 2.0 micrograms/kg). However, at the two
highest doses (1.0 and 2.0 micrograms/kg), TCDD increased epididymal transit
rate of sperm through the tail of the epididymis by 33 and 37%, respectively.
In contrast, primarily due to decreased transit rate (39%) of sperm through the
head plus body of the epididymis. I3C (1 mg/kg) significantly increased total
epididymal transit time by 31%. In conclusion, perinatal exposure of pregnant
rats to I3C, an Ah receptor agonist similar to TCDD, causes reproductive
abnormalities in male rat offspring; however, I3C and TCDD elicited both common
and different responses.

Unique Identifier: 97075286

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Acta Otorrinolaringol Esp 1996 Jul;47(4):306-310

[Papillomas in otorhinolaryngology: clinics, diagnostics and treatment].

[Article in Spanish]

Lopez Amado M, Lozano Ramirez A, Labella Caballero T

Catedra de ORL, Facultad de Medicina, Santiago de Compostela (La Coruna).

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.

Unique Identifier: 97070065

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Nutr Cancer 1996;25(3):249-257

Dietary retinoic acid inhibits mouse skin carcinogenesis irrespective of age at

initiation.

De Luca LM, Tarone R, Huynh M, Jones CS, Chen LC

Differentiation Control Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

In the two-stage protocol of skin carcinogenesis, the carcinogen
7,12-dimethylbenz[a]anthracene (DMBA) is applied to the skin of mice at around
seven weeks of age. We previously performed DMBA initiation at three weeks of
age to study the effect of pharmacological (30 micrograms/g diet) dietary
retinoic acid (RA) on skin carcinogenesis. In this study we asked whether
dietary pharmacological RA is equally effective against skin carcinogenesis
when mice are initiated with (DMBA) at 7 weeks of age and then subjected to
weekly applications of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate
(TPA) or mezerein (MEZ) for 20 weeks. Similar to the three-week initiation
protocol, high dietary RA inhibited papilloma incidence and yield in MEZ- but
not in TPA-promoted female SENCAR mice. In addition, carcinoma incidence and
yield were decreased by high dietary RA in TPA- as well as MEZ-treated mice.
These data demonstrate that the high dietary RA diet is as effective in
inhibiting papilloma and carcinoma formation when the DMBA is applied at seven
weeks of age as at three weeks.

Unique Identifier: 96367454

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Otolaryngol Head Neck Surg 1995 Oct;113(4):502-507

Laryngeal mask airway.

Sofferman RA, Johnson DL, Krag DN

Division of Otolaryngology, University of Vermont School of Medicine, Burlington, USA.

[No abstract available]

Unique Identifier: 96011743

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Vaccine 1995 Jan;13(1):72-76

Effect of imiquimod as an adjuvant for immunotherapy of genital HSV in guinea-pigs.

Bernstein DI, Harrison CJ, Tepe ER, Shahwan A, Miller RL

J.N. Gamble Institute of Medical Research, Cincinnati, OH 45219, USA.

Imiquimod, an immunomodulator which upregulates cell-mediated immune responses,
was evaluated as an adjuvant for immunotherapy of recurrent genital herpes
simplex virus (HSV) infection in guinea-pigs. In two experiments at separate
research centres, animals were immunized with HSV glycoprotein and either
placebo, 1 or 5 days of imiquimod, or complete Freund's adjuvant, 14 and 35
days after genital HSV-2 infection. Recurrent lesion days were then evaluated
from days 15-91. In both experiments, immunization with glycoprotein and
imiquimod most effectively reduced recurrence compared with unimmunized
controls (53-69%, p < 0.001-0.05). A peak reduction of 70-80% was observed
following the second immunization. This reduction was greater than that
provided by immunization with glycoprotein and complete Freund's adjuvant in
these experiments or those previously reported.

Unique Identifier: 95282494

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