[Microdebrider polypectomy and local corticosteroids]. / Polypectomie au microdébrideur et corticothérapie locale.

OBJECTIVES: To subjectively evaluate the efficiency and tolerance of polypectomy using the microdebrider followed by local corticosteroids in nasal polyposis (NP) after medical therapy failure. METHODS: Between 2000 and 2003, a polypectomy using the microdebrider was performed in 24 patients with NP. Efficiency was evaluated retrospectively by comparing pre- and postoperative functional and polyp scores. Efficiency was also evaluated regarding extension of NP on preoperative computed tomography (CT). Overall satisfaction was evaluated using a standardized phone questionnaire. RESULTS: Mean follow-up was 23.6+/-12.5 months. The overall and individual functional scores and the anatomical score were very significantly improved after polypectomy using the microdebrider. Extension of NP on preoperative CT was not related to polypectomy efficiency. Among the patients surveyed, 87.5% were globally satisfied, 73% considered the operative conditions as satisfactory, and 83% qualified the postoperative period as simple. CONCLUSION: Polypectomy using the microdebrider followed by local corticosteroids appears to be an efficient and well-tolerated treatment for improving functional symptomatology of patients with NP.

Matrix metalloproteinase-2 and -9 expression in sinonasal inverted papilloma.

STATEMENT OF PROBLEM: Inverted papilloma (IP) is a proliferative lesion of the epithelium lining the sinonasal tract, characterized by marked propensity for recurrence and association with carcinoma. To determine a putative role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the establishment of IP, their expression was studied in IP. METHODS: Archived surgical specimens from 15 IPs were studied using immunohistochemistry and compared to 12 nasal polyps (NP), a model of chronic respiratory mucosal inflammation, and to 6 control nasal mucosa (CM) samples obtained from snorers during turbinectomy. Within IP, MMP-2 and -9 expression was compared between tumoral areas with hyperplastic epithelium and non tumoral areas with nonhyperplastic epithelium. RESULTS: In IP, MMP-2 and MMP-9 epithelial expression was not different compared to CM and NP. MMP-9 expression in submucosal inflammatory cells was not different between IP and CM or NP. However, within IP, a significantly increased number of MMP-9 positive inflammatory cells in the lamina propria adjacent to the hyperplastic epithelium was observed compared to the lamina propria adjacent to nonhyperplastic epithelium. CONCLUSION: Our findings suggest that MMP 9 expressing inflammatory cells may be involved in the pathophysiology of IP.

[Efficacy of Derinox assessed with one PNIF (Peak Nasal Inspiratory Flow) in patients suffering from common cold]. / Efficacité de Dérinox chez des patients souffrant d'une rhinite virale évaluée par un PNIF (Peak Nasal Inspiratory Flow).

OBJECTIVES: The aim of this study was to compare the efficacy and tolerance of Dérinox (D) to Rhinofluimucil (R) and placebo (P) in the treatment of common cold, using an objective measure of nasal obstruction, the Peak Nasal Inspiratory Flow (PNIF--Clement Clarke International, Harlow, Angleterre). PATIENTS AND METHODS: This randomized, double-blind, double-dummy, parallel group study enrolled 354 patients (34 P, 165 D et 155 R) included by 85 general practitioners. The treatment duration was 5 days at usual recommended dosage regimens. PNIF measures were done before drug administration (T0) as well as 15 min and 3 h after each intake. Moreover, nasal obstruction, rhinorrhea and global discomfort were subjectively assessed. RESULTS: The efficacy of D was superior to that of P and R when comparing PNIF from T0 to T3 h after the first intake. At T15 min, rhinorrhea was significantly improved with both active treatments and global discomfort was significantly improved with D only. Treatment tolerance was satisfactory and comparable between the 3 groups. CONCLUSION: Efficacy of Dérinox(R) was superior to that of P and R for the improvement of the nasal obstruction (PNIF) between T0 and T3h (main criteria) after the first intake in patients suffering from common cold.

Smell dysfunction and related factors in diabetic patients.

OBJECTIVE: To analyze smell function in diabetic patients and healthy control subjects, with reference to individual characteristics and major complications of the disease. RESEARCH DESIGN AND METHODS: A cross-sectional study of smell recognition in 68 diabetic patients and 30 control subjects without known cause of smell impairment was conducted. Smell was studied using a kit of flavors that patients were asked to recognize, leading to a smell recognition score ranging from 0 (no recognition) to 20 (perfect recognition). Demographic and clinical data, and the electrogustometric threshold were recorded in both groups. Metabolic control and degenerative complications were studied in diabetic patients. RESULTS: The SRS was significantly lower in diabetic patients than in control subjects (12.4 +/- 0.5 vs. 15.1 +/- 0.5, P < 0.001). By use of univariate and multivariate analyses, this difference could not be explained by individual factors such as age, sex, body mass index, blood pressure, or tobacco or alcohol consumption but was related to diabetes. SRS correlated with EGT (r = 0.70, P < 0.001). In the diabetic group, SRS was associated with age (r = 0.29, P < 0.05), duration of diabetes (r = 0.27, P < 0.05), microalbuminuria (12.2 +/- 0.8 vs. 14.4 +/- 0.9, P < 0.05), peripheral neuropathy (10.3 +/- 1.0 vs. 14.1 +/- 0.9, P < 0.01), and EGT (r = 0.39; P < 0.001). By use of multivariate analysis, the strongest association was found with EGT (R2 = 0.15). CONCLUSIONS: These results suggest that smell recognition is impaired in patients with diabetes mellitus. Smell dysfunction is associated with age and degenerative complications of diabetes, suggesting a degenerative mechanism related to diabetes.

Taste impairment and related factors in type I diabetes mellitus.

To study taste in type I (insulin-dependent) diabetes mellitus, 57 consecutive diabetic outpatients (mean +/- SE duration of diabetes 11.4 +/- 0.4 yr) and 38 control subjects were screened for taste disorders with electrogustometry and chemical gustometry. Both groups were comparable for all subject characteristics except body mass index, which was higher in the diabetic group (P less than .05). A taste impairment was found in the diabetic group relative to the control group with electrogustometry (mean threshold 184.3 +/- 15.8 vs. 58.7 +/- 9.2 microA; P less than .001) and chemical gustometry (mean score 13.2 +/- 0.7 vs. 17.1 +/- 0.8; P less than .001). Hypogeusia was found among 73% of the diabetic patients versus 16% of the control subjects (P less than .001). The four primary tastes were involved in taste impairment. With multivariate analysis, taste disorders were related to diabetic status and tobacco and alcohol consumption. In the diabetic group, taste impairment was significantly associated with complications and duration of disease. With multivariate analysis, peripheral neuropathy had the strongest association with taste disorders. These results suggest that taste is impaired during the course of type I diabetes mellitus and that taste impairment could be a complication of the disease. A mechanism of the neuropathic type could be involved.

Definitive radiation treatment for early stage carcinoma of the soft palate and uvula: the indications for iridium 192 implantation.

From 1971 to 1984 59 T1 and T2 carcinomas of the soft palate and uvula were treated definitively by irradiation at the Henri Mondor hospital. Included are ten patients previously irradiated to the oropharyngeal area for either a carcinoma of the soft palate or another malignancy. Sixteen patients were treated by external irradiation alone, 14 by Iridium 192 implantation, and 29 by a combination of the two. Two techniques of implantation were used: the guide gutter technique (33 patients) and the plastic tube technique (10 patients). Clinically negative neck nodes (51/59) either received prophylactic telecobalt therapy (39/51) or were surveilled (12/51). Clinically involved nodes (8/59) were managed either by external irradiation alone (4/8) or combined with neck dissection (4/8). Local failure was 25% (4/16) after exclusive telecobalt therapy, 18% (5/19) after combined telecobalt therapy and implantation, and 0% (0/14) after Iridium 192 implantation alone. No local failures were seen with the plastic tube technique (0/10) as compared to 15% (5/33) for guide gutters. Only two nodal failures were observed (2/59: 3%). Crude 5-year disease-free survival was 33%. Severe complications were limited to one osteonecrosis, one soft tissue necrosis, and one partial palatal incompetence. Salivary impairment was reduced when implantation was used for part or all of the treatment. We recommend 45 Gy external radiation followed by 30 Gy from Iridium 192 implantation using the plastic tube method unless there has been prior oropharyngeal irradiation, in which case we give 60 Gy from implantation alone. For clinically negative neck nodes, we recommend 45 Gy prophylactic external neck irradiation. For clinically positive lymph nodes, this should be followed by either a 25 to 30 Gy boost to the involved nodes or a neck dissection.

Place of Iridium 192 implantation in definitive irradiation of faucial arch squamous cell carcinomas.

PURPOSE: We have reviewed the results of 165 T1 and T2 squamous cell carcinomas of the faucial arch treated by definitive irradiation including or not Iridium 192 brachytherapy to ascertain whether a significant relationship existed between Iridium implantation, local control, complications, and survival. METHODS AND MATERIALS: From March 1971 to November 1990, 58 T1 and 107 T2 (NO: 107/165; N1: 30/165; N2: 9/165; N3: 19/165) biopsy proven squamous cell carcinomas of the tonsillar region (104/165) and the soft palate and uvula (61/165) were treated in Henri Mondor Hospital by definitive irradiation with curative intent. From 1971 to 1981 (period 1), only guide gutter technique was available, so that implants were reserved for small tumors: patients were either managed by definitive telecobaltherapy to tumor site and neck node areas (Group 1; n = 48; mean dose: 70 Gy; confidence interval: +/- 5.5; 5 fractions of 1.8 Gy per week) or by exclusive Iridium implant (Group 2; n = 11; all T1NO; 64 Gy +/- 4.8) or by a combination of external beam radiation therapy to tumor site and neck nodes areas and Iridium implant (Group 3; n = 40). In 1981 (Period 2), a new plastic tube technique, which enables implantation of larger areas, was introduced in the department and all patients (Group 4; n = 66) were then managed by external radiation therapy (Group 3 + 4: 47 Gy +/- 4.3) followed by an Iridium implant (31 Gy +/- 10.5). Clinically positive neck nodes either received additional external dose with electrons or were excised. RESULTS: Overall 5-year survival (Kaplan Meier) was 21%, 50.5%, and 60% in groups 1, 2, and 3 + 4, respectively (p < 0.001, log rank). Five-year local control was 58%, 100%, and 91%, respectively (p < 0.001). Five-year necrosis rate was 4.5%, 20.5% and 18%, respectively (N.S.). Comparison of results between the two periods of the study (Group 1 + 2 + 3 vs. group 4) show that these two groups are statistically comparable according to site and size of tumor and N status and that both local control (77% vs. 94% at 5 years; p < 0.01) and disease-free survival (56% vs. 71%; p = 0.03) were improved after 1980, while there was a trend to an increase in overall survival (42% vs. 53% at 5 years; p = 0.08); nodal control (86% vs. 95% at 5 years), and necrosis rate (11% vs. 20% at 5 years) were not modified. Multivariate analysis showed that both local control (p < 0.0001) and overall survival (p < 0.0001) were improved when tumor was implanted. CONCLUSION: We recommend then to treat T1 and T2 squamous cell carcinomas of the faucial arch by external radiation therapy to tumor site and neck areas (45 Gy/25 fractions/5 weeks) followed by a 30 Gy Iridium implant and, for patients with clinically positive nodes, either a further 25-30 Gy electron beam irradiation to the nodes or neck node dissection.

Randomized study of 5 fluorouracil and cis platin as neoadjuvant therapy in head and neck cancer: a preliminary report.

A randomized prospective study of 5 fluorouracil (5-FU) and Cis platin preceding definitive local treatment for squamous cell carcinoma of the head and neck region was initiated in September 1986. Seventy-five patients were stratified by site (oral cavity-12, oropharynx-28, larynx-16, hypopharynx-19), and by Stage (Stage II-20, Stage III-43, Stage IV-12) and randomized to receive definitive local treatment (surgery and post-operative radiation or radiation alone) or chemotherapy followed by definitive local treatment. Chemotherapy consisted of three cycles of 120 hr 5-FU infusion 1 g/m2/day plus Cis platin 100 mg/m2 on day 1 on each cycle. Response to chemotherapy was complete in 17 patients (46%) for an overall response rate of 68%. All the patients have completed therapy with a median follow-up of more than 12 months. After local treatment, the complete response rate is 84% for the control group and 86% in the chemotherapy group. Actuarial disease-free survival at 1 year is 61% in the control group and 73% in the chemotherapy group (p = 0.25). These preliminary results show that in spite of initial tumor response, neoadjuvant chemotherapy does not improve long-term control and survival.

Iridium 192 implantation of T1 and T2 carcinomas of the mobile tongue.

Between 1970 and 1986, 166 patients with T1 or T2 epidermoid carcinomas of the mobile tongue were treated by iridium 192 implantation (70 T1N0, 83 T2N0, 13 T1-2 N1-3). Five-year actuarial survival was 52% for T1N0, 44% for T2aN0, and 8% for or T1-2 N1-3. Cause specific survivals were 90%, 71%, and 46%, respectively. Local control was 87% for both T1N0 and T2N0, and 69% for T1-2 N1-3. Seven of 23 failures were salvaged by surgery, increasing local control to 96% for T1 and 90% for T2. Thirty-six patients developed a minor or moderate necrosis (16% T1, 28% T2). Half of these involved bone but only five required surgical intervention. Both local control (LC) and necrosis (nec) increased with increasing dose but improvement beyond 65 Gy is minimal (less than or equal to 60 Gy: LC = 78% nec = 13%; 65 Gy: LC = 90% nec = 29%; greater than or equal to 70 Gy: LC = 94% nec = 23%). For N0 patients, neck management consisted of surveillance (n = 78), elective neck dissection followed with external irradiation for pathologically positive nodes (n = 72), or irradiation (n = 3). Clinically positive nodes (13 patients) were managed by either neck dissection followed by external irradiation if pathologically positive (n = 10) or irradiation alone (n = 3). Regional control was 79% for N0 patients, improving to 88% after surgical salvage, and was 9/13 for N1-3 patients. We recommend that T1 and T2 carcinomas of the mobile tongue be treated by iridium 192 implantation to deliver 65 Gy. Mandibular necrosis should be reduced by using an intra-oral lead-lined dental mold.

Stage I-II squamous cell carcinoma of the oral cavity treated by iridium-192: is elective neck dissection indicated?

This is a retrospective analysis of 233 evaluable patients with stage I-II squamous cell carcinoma of the oral cavity treated by definitive branchytherapy. Minimum follow-up is 3 years. Treatment of neck was chosen by a multidisciplinary team, according to age, medical status and availability for regular follow-up. One hundred and ten patients (47%) underwent elective neck dissection (END); 28 (25%) had positive nodes and received neck irradiation post-operatively. One hundred and twenty three patients (53%) were regularly followed up only, with therapeutic neck dissection (TND) reserved for cases of node relapses. In the END group, there were 19 neck relapses (17%): 12/60 (20%) in patients with mobile tongue carcinoma and 7/50 (14%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 9/19 (47%) cases. In the TND group, there were 21 neck relapses (17%): 16/82 (20%) in patients with mobile tongue carcinoma and 5/41 (10%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 13/21 (62%) cases. Ten-year survival is 37% for the END group and 31% for the TND group. Tumour stage and infiltration into underlying tissues increased the probability of neck relapse and death. Furthermore, a multivariate analysis showed that patients treated in the TND group had a higher probability of death than patients treated in the END group (p less than 0.04).

Six month administration of gelified intranasal insulin in 16 type 1 diabetic patients under multiple injections: efficacy vs subcutaneous injections and local tolerance.

OBJECTIVE: Nasal insulin administration is a potential route for intensive insulin management, less invasive and more rapid than subcutaneous injections. Previous studies have shown poor bioavailability (less than 15%) with nasal insulin administration with various absorption enhancers. The aim of the study was to evaluate in type 1 diabetic patients, the metabolic efficacy and local tolerance of a new gelified sprayed nasal insulin containing glychocolate and methylcellulose as absorption promoters. MATERIAL AND METHODS: The study was conducted in 16 type 1 diabetic patients (HbA1c 8.6+/-0.2%) in a cross-over trial including 2 six month randomized periods: a) NPH twice daily + 3 pre-prandial nasal insulin doses + nasal supplementation in case of unexpected hyperglycaemia; b) NPH twice daily + 3 pre-prandial regular insulin injections. End points were HbA1c levels, hypoglycaemic episodes and tolerance evaluated at month 0, 2, 6 and 8 on clinical symptoms and objective nasal assessments. RESULTS: Four patients were withdrawn because of nasal burning (3 cases) and persistent sinusitis (1 case), and one patient had purulent sinusitis at the month 6 examination. At month 6, HbA1c levels were comparable (8.3 +/- 0.1 vs 8.6 +/- 0.1%, m +/- SEM, NS) for nasal and subcutaneous period respectively. The number of hypoglycaemic events was identical during the 2 periods (88 episodes). Nasal tolerance with the gelified form was better than with the already reported lyophilized form but, when present, symptoms were more marked, suggesting a potentiating additional role of methylcellulose excipient on nasal intolerance. CONCLUSIONS: 1) Gelified nasal insulin is as efficient as subcutaneous regular insulin in type 1 diabetic patients. 2) Other galenic forms should be investigated to improve nasal tolerance and bioavailability.

Atypical sinusitis in adults must lead to looking for cystic fibrosis and primary ciliary dyskinesia.

UNLABELLED: HYPOTHESES/OBJECTIVES:: In adults, purulent pansinusitis or nasal polyposis starting early in life or that is permanently infected or associated either with chronic bronchial infection, infertility, or situs inversus are uncommon. In these atypical cases of chronic sinusitis (ACS), a primary dysfunction of the mucociliary clearance can be suspected. Adult patients with ACS were therefore investigated to detect primary ciliary dyskinesia (PCD) or cystic fibrosis (CF). STUDY DESIGN: Open, prospective study. PATIENTS AND METHODS: Forty-two patients with ACS were investigated with ciliary beat frequency and ultrastructure analysis in nasal cells and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis in blood leukocytes. RESULTS: The diagnosis of PCD was confirmed in seven (17%) patients. At least one CFTR gene mutation was detected in 16 (38%) patients. The diagnosis of CF was suggested in three (7%) compound heterozygous patients. Another 13 (31%) patients were heterozygous for a CFTR gene mutation or a complex allele. Comparison of clinical features of ACS showed that only a family history of chronic sinusitis (P <.01) or chronic bronchitis (P <.02) and the presence of diffuse bronchiectasis (P <.0001) or serous otitis media (P <.0001) were significantly more frequent in PCD patients than in patients carrying CFTR gene mutations or those without PCD or CFTR gene mutations. CONCLUSIONS: ACS should be considered a remarkable entity in which congenital abnormalities of epithelial cells are frequently detected (55% of patients). The higher frequency of mutations in ACS patients compared with the general population suggests that heterozygoty for CFTR gene mutation could be a sinusitis-causing status.

Myofibroblast accumulation induced by transforming growth factor-beta is involved in the pathogenesis of nasal polyps.

Myofibroblasts that express alpha-smooth muscle actin (alpha-SMA) are detected in many chronic inflammatory diseases. Transforming growth factor-beta (TGF-beta) is a potent inducer of myofibroblast accumulation in tissues. In this study, scattered myofibroblasts and TGF-beta were quantified and localized in nasal polyps (NPs) and normal nasal mucosa (NM). NPs were sampled in 16 patients during ethmoidectomy and NM was obtained from 10 control subjects during rhinoplasty. alpha-SMA and TGF-beta were detected using immunohistochemistry and the numbers of labeled cells were quantified (alpha-SMA and TGF-beta indices) and compared between NPs and NM. In eight NPs, in which the pedicle was preserved, alpha-SMA and TGF-beta were evaluated and compared in the pedicle, central, and tip areas. Finally, TGF-beta expression was compared between low (zone 1), moderate (zone 2), and high (zone 3) zones of alpha-SMA positivity. alpha-SMA and TGF-beta indices were significantly higher in NPs than in NM. In the eight selected NPs, alpha-SMA-positive cells were significantly more abundant in the pedicle than in the central and tip areas, whereas TGF-beta-positive cells were significantly more numerous in the pedicle than in the tip area. The number of TGF-beta-positive cells was significantly higher in zone 3 than in zone 1 of alpha-SMA positivity. Myofibroblasts, which are abundant in NPs but rare in NM, could be involved in the growth of NPs by inducing extracellular matrix accumulation. The local development of myofibroblasts in NPs could be controlled by TGF-beta, locally produced by inflammatory cells.

Epithelial cell proliferation in nasal polyps could be up-regulated by platelet-derived growth factor.

The modifications of epithelial differentiation and proliferation observed in nasal polyps (NP) could be related to local secretion of growth factors, among which platelet-derived growth factor (PDGF) could play a key role. We therefore prospectively studied, by immunohistochemistry, proliferating cell nuclear antigen (PCNA, an S-phase cell marker), PDGF, and CD-68 (activated macrophages marker) expression in NP and inferior turbinate mucosa (NM) in 11 patients. Our data show that PCNA and PDGF expression are increased in NP epithelium, while CD-68 expression is increased in NP epithelium and lamina propria when compared to NM. Increased local PDGF secretion by numerous activated macrophages could therefore be involved in epithelial cell proliferation up-regulation in NP. PDGF could also be involved in the pathogenesis of NP via its connective tissue remodeling actions.

Radiofrequency is a safe and effective treatment of turbinate hypertrophy.

OBJECTIVE: To evaluate the safety and efficacy of radiofrequency for reduction of inferior turbinate volume. STUDY DESIGN: Prospective before-and-after trial. METHODS: Fourteen patients complaining of chronic nasal obstruction and failing to respond to medical treatment were prospectively enrolled. All patients presented with inferior turbinate hypertrophy and no septal deformity. Radiofrequency inferior turbinate tissue reduction with three punctures in each turbinate (mean energy/puncture: 342 +/- 36 J, mean duration: 69 +/- 17 s, plateau tissue temperature: 75 +/- 6.4 degrees C). Patients were evaluated before and on days 3, 7, and 60 after intervention. RESULTS: No postoperative pain or complications were reported. Evaluation of nasal obstruction, quantified by visual analogue scale, showed a significant decrease of day time and nighttime obstruction after surgery. Acoustic rhinometry measurements showed that turbinate hypertrophy was significantly reduced in the sitting and supine positions on day 60 after surgery. Saccharin transit times decreased significantly on day 60 compared with preoperative measurements. Ciliary beat frequency, measured in vitro in nasal epithelial cells sampled from the inferior turbinate by brushing, was not significantly different before surgery and on day 60 after surgery. In the same samples, ciliated cells were the most abundant epithelial cell type before and after surgery, although in five cases, moderate numbers of squamous cells were detected on either day 7 or day 60 after surgery. CONCLUSION: Radiofrequency is a safe surgical procedure capable of reducing turbinate volume without altering the nasal mucosa, and causing minimal discomfort for the patient.

Nasal cavity geometry measured by acoustic rhinometry and computed tomography.

OBJECTIVE: To determine the significance of cross-sectional areas obtained by acoustic rhinometry. DESIGN: Comparison of data obtained by acoustic rhinometry and computed tomography (CT). SETTING: Outpatient clinic. PATIENTS: Nine adults with nasal obstruction due to turbinate hypertrophy. MAIN OUTCOME MEASURES: Acoustic rhinometry and CT were performed after nasal decongestion. The acoustic area-distance curve was analyzed based on 3 notches (A1, A2, and A3) corresponding to 3 local minimal areas. Computed tomographic measurements were made in the coronal plane at 0.5-cm intervals, and the narrowest sections in the anterior (S1), middle (S2), and posterior (S3) parts of the nasal cavity were selected. Mean specific section areas and volumes were computed by integration of the acoustic area-distance curves using the same procedure for the 2 methods. RESULTS: Significant correlations were found between acoustic and CT areas in the anterior nasal cavity (A1 vs S1, P < .001; A2 vs S2, P < .005). Acoustic and CT anterior volumes from A1 to A2 and from S1 to S2 were significantly correlated with each other (P < .005). No correlation was found between acoustic and CT areas measured at the posterior part of the nose (A3 vs S3). A weak correlation was evidenced between acoustic and CT posterior volumes from A2 to A3 and from S2 to S3 (P < .05). CONCLUSIONS: Acoustic rhinometry may be particularly well suited to the evaluation of anterior nasal geometry during clinical studies. At the posterior part of the nose, acoustic measurements may be of limited clinical relevance.

Expression of the transforming growth factor beta isoforms in inflammatory cells of nasal polyps.

OBJECTIVE: To determine the expression and the potential role of transforming growth factor beta (TGF-beta) in nasal polyposis. DESIGN: Comparison of TGF-beta expression between normal and inflammatory nasal mucosa and polyps; in inflammatory nasal polyps, characterization of the TGF-beta isoforms expression and their potential location in macrophages and eosinophils. SETTING: Patients and samples were selected at the Hôpital Intercommunal, Créteil, France, and immunohistochemistry and immunoblots were performed at the Institut National de la Sante et de la Recherche Medicale U296 (Universite Paris XII, France). SUBJECTS: Nasal polyps and nasal mucosa were sampled in 21 patients during ethmoidectomy, and muscosa was sampled in 6 healthy patients during rhinoplasty. METHODS: Immunohistochemistry and Western blot analysis were performed using specific antibodies to TGF-beta1-3, TGF-beta1, TGF-beta2, and TGF-beta3 isoforms. Double labeling was also performed using anti-TGF-beta1 antibody together with macrophages or eosinophil-specific antibodies. RESULTS: The expression of TGF-beta(1-3) was significantly higher in inflammatory nasal polyps than in inflammatory nasal mucosa and higher in inflammatory nasal mucosa than in nasal mucosa from healthy patients. Transforming growth factor beta1 was the main isoform detected in inflammatory nasal polyps, and it was present in numerous macrophages and in some eosinophils. CONCLUSIONS: Transforming growth factor beta, mainly TGF-beta1, is strongly expressed in inflammatory nasal mucosa, where it could be produced by macrophages and eosinophils. Transforming growth factor beta could induce epithelium and connective tissue modifications and therefore be involved in the pathogenesis of nasal polyposis.

Increased epithelial cell proliferation in nasal polyps.

OBJECTIVE: To detect, quantify, and compare respiratory epithelial cell proliferation in nasal mucosa and polyps from patients with nasal polyposis. DESIGN: Cohort study. SETTING: Patients and samples were selected at the Hôpital Intercommunal de Créteil (France). Flow cytofluorometry and immunohistochemistry were performed at Hôpitaux Tenon and Mondor (Université Paris [France] VI et XII). PATIENTS: Twenty-one patients undergoing endoscopic ethmoidectomy for treatment of nasal polyposis. METHODS: In 10 cases, epithelial cells were removed from frozen inferior turbinate mucosa and polyps by mechanical disaggregation and were then analyzed by flow cytofluorometry, providing the cell DNA content (propidium iodide labeling) and the percentage of S-phase cells. In 11 cases, inferior turbinate mucosa and polyps were fixed in formaldehyde and embedded in paraffin. Proliferating cell nuclear antigen expression in the epithelium was quantified by immunohistochemistry; a proliferating cell nuclear antigen index was calculated for each sample in the basal area, suprabasal area, and full height of the epithelium. RESULTS: All cell populations studied were diploid, and percentages of S-phrase cells were significantly higher in nasal polyps than in mucosa. Proliferating cell nuclear antigen indexes were significantly higher in nasal polyps than in the suprabasal area and full height of the mucosal epithelium. CONCLUSION: Cell proliferation is increased in epithelium from nasal polyps. Epithelial damage caused by inflammatory mediators could induce this increased cell proliferation via epithelial repair processes. Inflammatory cells could up-regulate epithelial cell proliferation by secreting growth factors.

Central retinal vein occlusion and sudden deafness: a possible common pathogenesis.

CASE REPORT: A 31-year-old woman complained of blurred vision in the right eye due to a well-perfused central retinal vein occlusion (CRVO) and two months later, of sudden deafness (SD) in her right ear. Her visual acuity and hearing recovered almost completely within a few months. Medical evaluation disclosed the combination of slight coagulation abnormalities (moderate decrease in protein S, slightly elevated lipoprotein (a)), and elevated fibrinogen, with plasma hyperviscosity. DISCUSSION: The occurrence of CRVO then SD suggests that the same underlying conditions can be considered as risk factors for both diseases and shows up some similarities in the pathogenesis of these acute impairments of microvascular blood flow in the retina and the cochlea.

[Initial polychemotherapy in the treatment of cancers of the head and neck. The efficacy and tolerance of 2 nonrandomized combinations in 48 patients]. / Polychimiothérapie initiale dans le traitement des cancers des voies aérodisgestives supérieures. Efficacité et tolérance de deux associations non randomisées chez 48 patients.

Before loco regional treatment for head and neck cancer forty eight patients received one or the other of the following combined chemotherapy regimens: Regimen A (28 patients): high dosage methotrexate, bleomycin, cis-platin; regimen B (20 patients): common dosage methotrexate, bleomycin, hydroxyurea, vincristin. The effectiveness of regimen A seemed better than that of regimen B (46% responses versus 20%). This assessment must be accepted with caution, since, although the organization of treatment was strictly similar in the two groups, the study was not randomized, and there were noticeable differences between the two groups. Regimen B was associated with no toxicity. Regimen A was responsible for two fatalities. These two cases were linked to high dosage methotrexate. However, a combined chemotherapy regimen of type A with the high dosage methotrexate replaced by intermediate dosage methotrexate, seems feasible to us. Loco regional treatment was not impaired by initial chemotherapy with either regimen.