RRP Medical Reference Service
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
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:
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Marshfield WI 54449
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
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
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
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
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
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
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
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
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
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
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,
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
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
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
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
Nurse Pract 1997 Apr;22(4):24-25
Human papillomatous virus infection update: impact on women's health.
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.
Comment in: Nurse Pract 1997 Aug; 22(8):19, 22
Unique Identifier: 97274911
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
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
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
Nutr Cancer 1996;25(3):249-257
Dietary retinoic acid inhibits mouse skin carcinogenesis irrespective of age at
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
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
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
P.O. Box 6643
Lawrenceville NJ 08648-0643