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Ilana Doweck

idoweck@netvision.net.il

Journal articles

2008
 
DOI   
PMID 
Ilana Doweck, K Thomas Robbins, Sandeep Samant, Francisco Vieira (2008)  Intra-arterial chemoradiation for T3-4 oral cavity cancer: treatment outcomes in comparison to oropharyngeal and hypopharyngeal carcinoma.   World J Surg Oncol 6: 01  
Abstract: BACKGROUND: Surgery followed by radiotherapy is the standard of care for resectable locally advanced oral cavity squamous cell carcinoma (SCC). We report the treatment outcomes of patients with T3-T4 SCC of the oral cavity treated with chemoradiation, an alternative approach. PATIENTS AND METHODS: From a series of 240 patients with stage III-IV carcinoma of the upper aerodigestive tract who were treated consecutively according to the RADPLAT protocol, a subset analysis of 155 patients with T3-T4 SCC (Oral cavity SCC N = 22, oropharynx SCC N = 94 and hypopharynx SCC N = 39), was performed. The goal was to test the hypothesis that oral cavity SCC treated with chemoradiation has similar outcomes to the two comparison sites. RESULTS: With a median follow-up of 58 months, local disease control was 69% and the overall survival was 37%. In comparison, local disease control for the oropharynx and hypopharynx groups was 86% and 79% respectively. The overall survival rate for the oropharyngeal and hypopharyngeal groups were 41% and 6% respectively CONCLUSION: Patients with locally advanced oral cavity cancer treated with the chemoradiation protocol RADPLAT have outcomes that are equal or better compared to patients with similar disease involving the oropharynx and hypopharynx.
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DOI   
PMID 
Yoav Yanir, Ilana Doweck (2008)  Regional metastases in well-differentiated thyroid carcinoma: pattern of spread.   Laryngoscope 118: 3. 433-436 Mar  
Abstract: OBJECTIVES/HYPOTHESIS: To determine the pattern of spread of WDTC to regional lymph nodes, in patients who presented with clinically positive nodes. STUDY DESIGN: Retrospective chart review. MATERIALS AND METHODS: Between October 2001 and December 2006, a total of 27 consecutive patients (12 males, 15 females) with clinical evidence of cervical metastasis of well-differentiated thyroid carcinoma (WDTC) underwent 28 neck dissections (ND) with a mean follow-up 33.7 months. Papillary carcinoma was found in 24 patients and follicular carcinoma in 3.All neck dissection specimens were separated during surgery into levels, and analysis was done with respect to the levels of the neck.Clinical and demographic parameters were correlated to the pathologic parameters, including number of pathologic nodes, size of tumor, and the patient's age, with univariate and multivariate analysis. RESULTS: The mean number of pathologic nodes in ND specimen was 6.7. The predominant site of metastasis was level VI (95%), followed by level III (68%), level IV (57%), and level II (54%). Metastases above the XI nerve were found in 7% of the patients. Level V showed 20% of nodal metastasis. A correlation was found between size of primary tumor and number of positive pathologic lymph nodes (P = .02) and an inverse correlation between the age of the patient and the number of pathologic nodes (P = .043). CONCLUSIONS: The high incidence of metastatic disease in levels II through VI supports the recommendation for posterolateral and anterior ND in patients with WDTC and clinically positive nodes. The correlation between tumor size, the age of the patient, and the number of positive nodes is an interesting finding that warrants further study.
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2006
 
DOI   
PMID 
Ilana Doweck, Victoria Kaplan-Cohen, Inna Naroditsky, Edmond Sabo, Neta Ilan, Israel Vlodavsky (2006)  Heparanase localization and expression by head and neck cancer: correlation with tumor progression and patient survival.   Neoplasia 8: 12. 1055-1061 Dec  
Abstract: Heparanase is an endoglycosidase that specifically cleaves heparan sulfate (HS) side chains of HS proteoglycans, the major proteoglycans in the extracellular matrix and cell surfaces. Traditionally, heparanase activity was implicated in cellular invasion associated with angiogenesis, inflammation, and cancer metastasis. More recently, heparanase upregulation was documented in an increasing number of primary human tumors, correlating with reduced postoperative survival rate and enhanced tumor angiogenesis. In the present study, we examined the expression of heparanase in squamous cell carcinoma of the head and neck by means of immunostaining, and we correlated expression levels with patient outcome. The intensity and extent of heparanase staining correlated with tumor stage (P = .049 and P = .027, respectively), and the extent of staining further correlated with tumor grade (P = .047). Moreover, heparanase expression inversely correlated with patient status at the end of the study (P = .012). Notably, heparanase localization was found to be an important parameter for patient status. Thus, 63% of patients with nuclear staining, compared to 19% of patients with cytoplasmic staining (P = .0043), were alive, indicating that nuclear localization of the enzyme predicts a favorable outcome.
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DOI   
PMID 
Arie Gordin, Marcello Daitzchman, Ilana Doweck, Nikolay Yefremov, Avishay Golz, Zohar Keidar, Rachel Bar-Shalom, Abraham Kuten, Ora Israel (2006)  Fluorodeoxyglucose-positron emission tomography/computed tomography imaging in patients with carcinoma of the larynx: diagnostic accuracy and impact on clinical management.   Laryngoscope 116: 2. 273-278 Feb  
Abstract: OBJECTIVES: The objectives of this study were to assess the value of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with carcinoma of the larynx as compared with PET and CT alone and to assess the impact of PET/CT on further clinical management. STUDY DESIGN: This was a prospective, nonrandomized study. MATERIALS AND METHODS: Forty-two patients with laryngeal cancer had 51 PET/CT examinations. There were 34 men and eight women, aged 39 to 80 years. All studies were interpreted prospectively with knowledge of the clinical history and results of previous imaging tests. The performance of different imaging modalities was compared on both a study- and lesion-based analysis for sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and accuracy. Changes in patient care resulting from the PET/CT studies were recorded. RESULTS: The study analysis showed that PET/CT had a sensitivity of 92%, specificity 96%, PPV 96%, NPV 92%, and accuracy of 94% as compared with 92%, 73%, 76%, 91%, and 82% for PET, and 88%, 8%, 48%, 40%, and 51% for CT, respectively. There were 112 suspicious sites evaluated in the 51 studies. PET/CT altered management in 25 patients (59%) by sparing previously planned diagnostic procedures (n=13), by changing the planned therapeutic approach (n=9), and by guiding a biopsy to a metabolically active laryngeal area (n=3). CONCLUSIONS: The performance of PET/CT is better than standalone PET or CT in patients with cancer of the larynx. PET/CT had a major impact on management of 59% of patients.
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2005
 
DOI   
PMID 
Geva Barzilai, Elhanan Greenberg, Raanan Cohen-Kerem, Ilana Doweck (2005)  Pattern of regional metastases from cutaneous squamous cell carcinoma of the head and neck.   Otolaryngol Head Neck Surg 132: 6. 852-856 Jun  
Abstract: OBJECTIVE: To assess the pattern of regional metastases from SCC of the skin of the head and neck as a prognostic factor. STUDY DESIGN AND SETTING: A retrospective chart review of 22 patients treated in a tertiary academic center. RESULTS: Metastases could be assessed clinically in the parotid gland and the neck in 50% and 59% of the patients, respectively. Histologic examination showed metastases in the parotid gland and the neck in 68% and 45.5%, respectively. Occult disease was 36% and 20% in the parotid gland and neck, respectively. The 1st echelon for metastasis was the parotid gland lymph nodes, whereas level II lymph nodes were the 1st echelon in the neck. Metastases to both the parotid gland and neck decreased the overall survival to 0, compared with 60% for metastases to the parotid gland and 100% for the neck. CONCLUSIONS: SCC of the skin of the head and neck with regional metastases has a high incidence of occult metastases in the parotid gland and the neck. Patients with metastases in both sites have a poor prognosis.
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DOI   
PMID 
K Thomas Robbins, Ilana Doweck, Sandeep Samant, Francisco Vieira (2005)  Effectiveness of superselective and selective neck dissection for advanced nodal metastases after chemoradiation.   Arch Otolaryngol Head Neck Surg 131: 11. 965-969 Nov  
Abstract: OBJECTIVE: To determine the efficacy of selective and superselective neck dissection for patients with bulky or residual nodal metastasis treated with concomitant intra-arterial cisplatin and radiotherapy. DESIGN: Prospective study. SETTING: University of Tennessee, Memphis. PATIENTS: A total of 240 patients with stage III or IV head and neck squamous cell carcinoma. INTERVENTIONS: Treatment with cisplatin, 150 mg/m2 intra-arterially, and sodium thiosulfate, 9 g/m2 intravenously, weekly for 4 weeks; and radiotherapy, 2 Gy per fraction per day, 5 times weekly, for a total of 68 to 74 Gy over 6 to 7 weeks. MAIN OUTCOME MEASURES: Regional control, distant metastases, and overall survival for patients undergoing radical or modified radical neck dissection (n = 12), selective neck dissection (n = 65), and superselective neck dissection (levels II-III only) (n = 7). RESULTS: Among the total group of 240 patients, 106 neck dissections were performed on 84 patients who had bulky nodal disease. With a median follow-up of 58 months (range, 12-96 months), regional failure occurred in 11 (4.6%) of 240 patients: 2 (17%) of the 12 who had modified radical neck dissection, 3 (5%) of the 65 who had selective neck dissection, none of the 7 patients who had superselective neck dissection, and 6 (4%) of the 156 who had no neck dissection. The rates of overall survival and distant metastases were not significantly different among the 3 neck dissection subsets. CONCLUSION: Selective and superselective neck dissection, which spare function and minimize morbidity, are viable therapeutic alternatives for patients with residual disease confined to 1 level after intra-arterial chemoradiation treatment, and possibly for other chemoradiation protocols.
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2004
 
PMID 
K Thomas Robbins, Ilana Doweck, Sandeep Samant, Francisco Vieira, Parvesh Kumar (2004)  Factors predictive of local disease control after intra-arterial concomitant chemoradiation (RADPLAT).   Laryngoscope 114: 3. 411-417 Mar  
Abstract: OBJECTIVES: To determine the relative risk of prognostic factors for local disease control following RADPLAT. STUDY DESIGN: Prospective study, academic medical center. METHODS: Analyses of nine categories of risk factors among 240 patients with Stage II-IV carcinoma consecutively treated with RADPLAT (cisplatin 150 mg/m IA and sodium thiosulfate 9 g/m IV, weekly x4; radiotherapy 2 Gy/fraction/d, 5x weekly, 68-74 Gy over 6 to 7 weeks). Median follow-up: 58 months (range, 12-96 mo). RESULTS: The percentage of patients who had local disease control was 87.5%. Univariant analysis showed T classification (P =.01), laterality of neck disease (P =.026), number of neck levels involved (P =.008), total dose of radiation greater versus less than 60 Gy (P =.027), and presence of pathologically positive lymph nodes following chemoradiation (P =.01) to be significant. Logistic regression analysis showed total dose of radiation (P =.03) and the presence of pathologically positive lymph nodes following chemoradiation (P =.05) to be significant. For Kaplan-Meier estimates of local disease control at 5 years, T classification (P =.038), number of levels with nodal disease (P =.006), and total dose of radiation therapy (P =.0001) were significant. The log-rank test identified as significant the total dose of radiation therapy (P <.0001), the presence of pathologically positive lymph nodes following chemoradiation (P =.005), and the number of neck levels with positive nodes (P =.006). The Cox regression model showed significance for the total dose of radiation (P =.001), the presence of pathologically positive lymph nodes following chemoradiation (P =.007), and the T classification (P =.029). CONCLUSION: Risk factors significantly associated with local disease control after RADPLAT appears to differ from more traditional therapy and is suggestive of a paradigm shift.
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2003
 
PMID 
Nechama Uri, Raanan Cohen-Kerem, Irit Elmalah, Illana Doweck, Elhanan Greenberg (2003)  Classification of fungal sinusitis in immunocompetent patients.   Otolaryngol Head Neck Surg 129: 4. 372-378 Oct  
Abstract: OBJECTIVE: The objective of this study was to review the subgroup classification of fungal sinusitis in immunocompetent patients. METHODS: The study design included 19 immunocompetent patients with fungal sinusitis who were operated on between 1993 and 1998. RESULTS: Ten of 19 patients showed a fungus ball. They underwent a limited surgical endoscopic procedure, and no further treatment was needed. Four patients had allergic fungal sinusitis and were treated postoperatively with irrigation, topical steroids, and oral steroids in 2 patients as well. Five patients had chronic sinusitis with significant bone erosion. All 5 underwent an extensive endoscopic procedure and were treated postoperatively by repeated irrigation, endoscopic cleaning, and no antifungal preparation. Two patients of this group are reported broadly. CONCLUSIONS: Fungal sinusitis in immunocompetent patients is not a rare condition and can be divided into 3 categories: 1) fungus ball, 2) chronic erosive (noninvasive) fungal sinusitis, and 3) allergic fungal sinusitis. The symptomatology, treatment, and prognosis varied significantly among the 3 different categories.
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PMID 
Nechama Uri, Elhanan Greenberg, Ruth Kitzes-Cohen, Ilana Doweck (2003)  Acyclovir in the treatment of Ramsay Hunt syndrome.   Otolaryngol Head Neck Surg 129: 4. 379-381 Oct  
Abstract: Ramsay Hunt syndrome is an herpetic disease with ominous prognosis regarding the facial nerve. Treatment with acyclovir, a well-known virostatic agent, has been given in a small number of patients in recent years with excellent results. We report on the administration of acyclovir intravenously for 7 days in 31 patients with Ramsay Hunt syndrome, with overall recovery rate of 82.6%. There were no side effects regarding this treatment.
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DOI   
PMID 
Ilana Doweck, K Thomas Robbins, William M Mendenhall, Russell W Hinerman, Christopher Morris, Robert Amdur (2003)  Neck level-specific nodal metastases in oropharyngeal cancer: is there a role for selective neck dissection after definitive radiation therapy?   Head Neck 25: 11. 960-967 Nov  
Abstract: PURPOSE: To determine the extent of the required neck dissection for patients with persistent lymphadenopathy after definitive radiation therapy for oropharyngeal cancer. If feasible, a conservative approach using selective neck dissection would likely minimize the extent of neck fibrosis and other adverse sequelae. METHODS: Analysis of pretreatment and posttreatment radiologic scans and pathology reports of 76 patients with oropharyngeal carcinoma (35 tonsil; 41 base of tongue), who had radiologic evidence of persistent nodal disease for level-specific involvement. Patients were treated with twice-daily fractionations of external-beam radiation therapy (median dose, 76.8 Gy to the primary tumor) and planned neck dissection (levels I-V) for bulky nodes (N2-3) or salvage neck dissection for N1 disease. RESULTS: The distribution of clinical nodal disease by neck level on the basis of pretreatment and posttreatment radiologic scans indicated levels II and III to be most commonly involved. The false-negative rate for the restaging radiologic scans for each neck level was as follows: level I, 0%; level II, 8%; level III, 6%; level IV, 5%; and level V, 1.5%. Of the eight hemi-necks found to contain positive pathologic nodes in a neck level judged to be negative on the basis of restaging scans, five of the patients subsequently had disease recurrence in the primary site. Patients who had evidence of residual neck disease had a significantly lower rate of locoregional control (77% vs 100%, p =.0005). CONCLUSIONS: The extent of neck dissection for patients with nodal disease associated with oropharyngeal cancer treated with radiation therapy should include levels II-IV. It is reasonable to spare levels I and V in patients without radiologic and clinical evidence of positive nodes in levels I and V.
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PMID 
Carlos R Gordon, Ilana Doweck, Zohar Nachum, Adi Gonen, Orna Spitzer, Avi Shupak (2003)  Evaluation of betahistine for the prevention of seasickness: effect on vestibular function, psychomotor performance and efficacy at sea.   J Vestib Res 13: 2-3. 103-111  
Abstract: Betahistine was evaluated for the prevention of seasickness in a laboratory and sea study. The effect of 48 mg betahistine on the vestibulo-ocular reflex (VOR) and on psychomotor performance was evaluated in twelve young healthy subjects in a double-blind, placebo controlled, randomized, crossover design. The vestibulo-ocular reflex was evaluated by the Sinusoidal Harmonic Acceleration (SHA) test at frequencies of 0.01, 0.02, 0.04, 0.08 and 0.16 Hz. Psychomotor performance was assessed by both computerized and paper and pencil test batteries. No significant differences in VOR gain or phase were found between betahistine and placebo treatment for any of the frequencies tested. No significant differences were found between treatments for any of the psychomotor performance tests or other possible side effects. The effect of 48 mg betahistine on seasickness severity was evaluated in 83 subjects during a voyage in rough seas. Betahistine had a borderline non-statistically significant effect on the prevention of seasickness in comparison with placebo (p = 0.053), with no notable side effects. Although our results are insufficient to recommend betahistine as an anti-seasickness drug, further studies are required to determine its possible effectiveness in less provocative motion sickness situations.
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PMID 
Nechama Uri, Ilana Doweck, Raanan Cohen-Kerem, Elhanan Greenberg (2003)  Acyclovir in the treatment of idiopathic sudden sensorineural hearing loss.   Otolaryngol Head Neck Surg 128: 4. 544-549 Apr  
Abstract: BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a vexing problem that continues to pose a diagnostic and therapeutic enigma for the otologist. The aim of the study, adopting the viral theory, was to discover whether patients with ISSNHL would benefit from early treatment with acyclovir and hydrocortisone compared with patients treated by hydrocortisone alone. METHODS: Sixty patients with ISSNHL were treated in a prospective controlled randomized manner. Patients were seen within 7 days of onset and were divided randomly into 2 groups. The study group patients were treated with acyclovir and hydrocortisone, whereas those in the control group were treated with hydrocortisone alone. RESULTS: We compared the 2 groups before and after treatment regarding SRT, mean hearing level at each frequency, speech reception threshold improvement, gender, age, tinnitus, and balance complaints. The overall improvement was 78%. CONCLUSION: We conclude that there probably is no benefit from the addition of acyclovir in the treatment of ISSNHL.
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2002
 
PMID 
Ilana Doweck, Douglas Denys, K Thomas Robbins (2002)  Tumor volume predicts outcome for advanced head and neck cancer treated with targeted chemoradiotherapy.   Laryngoscope 112: 10. 1742-1749 Oct  
Abstract: OBJECTIVES/HYPOTHESIS: Just as tumor volume is a prognostic indicator for local disease control among patients with head and neck cancer of intermediate size treated with radiation therapy, we hypothesized a similar association for patients with advanced disease treated with chemoradiation therapy. STUDY DESIGN: Retrospective analysis of primary and nodal tumor volume was correlated with prospectively collected treatment outcome measures. METHODS: Sixty-four patients with stage III-IV disease who were treated with targeted intra-arterial chemotherapy and radiation therapy (RADPLAT) were studied. Tumor volume was correlated with local disease control and survival.RESULTS Primary tumor volume correlated with local disease control and survival. The greatest risk for local failure was found among patients with primary tumor volume greater than 19.6 cc (93.8% vs. 57% [P =.001]). A nominal logistic regression analysis demonstrated primary tumor volume as being the only significant parameter related to local failure. Survival was only 14.1% among patients with primary tumor volume greater than 19.6 cc compared with 41.5% for patients with volumes less than 19.6 cc ( P=.0018). A proportional hazard model indicated that the most significant and independent parameters associated with survival were primary tumor volume ( P=.0007) and the site of the tumor ( P=.05). CONCLUSION: Tumor volume is the most important factor predictive of treatment outcome among patients with advanced head and neck cancer and should be used to stratify favorable versus unfavorable patient subsets.
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PMID 
Nechama Uri, Raanan Cohen-Kerem, Geva Barzilai, Elhanan Greenberg, Ilana Doweck, Daniel Weiler-Ravell (2002)  Functional endoscopic sinus surgery in the treatment of massive polyposis in asthmatic patients.   J Laryngol Otol 116: 3. 185-189 Mar  
Abstract: The association between asthma and sinonasal disease has been known for years. Effective treatment of sinonasal disease, which is one of the factors that exacerbate asthma, may also improve and stabilize the asthmatic condition. This study examines the outcome of functional endoscopic sinus surgery (FESS) on asthmatic patients with massive nasal polyposis. Thirty-four asthmatic patients were included in the study. All were operated on in our department and were analysed for pre-operative data regarding their asthma and sinonasal disease. A questionnaire regarding subjective evaluation of asthma and sinonasal status was presented to the patients, and objective evaluations, including nasal endoscopy and spirometry, were performed. Follow-up endoscopy revealed satisfactory results in 88 per cent, with positive correlation to the patients' subjective assessment of nasal status. No such correlation was found with regard to subjective and objective assessment of asthma: a small group of patients had completely clean sinonasal cavities with no perceived improvement in their asthmatic condition. The use of prednisolone and bronchodilators was significantly reduced post-operatively. However, in a subgroup of 13 patients followed at the asthma clinic, who had adequate pre-operative and post-operative data, there was no difference in their pre- and post-operative asthma condition. Seven had minimal improvement and in six there was a definite worsening of their asthma; nevertheless, nasal breathing and quality of life improved in most patients. The mean follow-up was 2.1 years. Thus, we conclude that in this study FESS does not improve asthma, but does improve the quality of the life of the patient.
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PMID 
Raanan Cohen-Kerem, Nitza Lahat, Irit Elmalah, Elhanan Greenberg, Murray B Resnick, Ilana Doweck, Michal A Rahat (2002)  Detection of cytokeratins in normal and malignant laryngeal epithelia by means of reverse transcriptase-polymerase chain reaction.   Ann Otol Rhinol Laryngol 111: 2. 149-154 Feb  
Abstract: Cytokeratins (CKs) are a subgroup of intermediate filament proteins that take part in forming the cytoskeleton. The epithelial cells in different organs express distinct CKs, and this expression may be modified during malignant transformation. Here we describe the use of reverse transcriptase-polymerase chain reaction followed by Southern blotting to determine the profile of expression of CKs in both normal and malignant laryngeal samples. Thirty-six samples were subjected to histologic examination and classified as 17 squamous cell carcinomas, 3 dysplastic lesions, and 16 normal samples. CK8 and CK19 were expressed in almost all samples, both cancerous and normal, and were therefore used to verify the integrity of RNA. Expression of CK2, CK9, and CK20 was not detected in any of the samples, normal or cancerous. CK15 and CK18 showed low sensitivity for detection of cancer (36.4% and 45.5%, respectively). CK10 showed relatively high sensitivity (91%), but only moderate specificity (69.2%). Only CK17 showed both high sensitivity and specificity (91% and 92.3%, respectively; positive predictive value, 91%). We propose that CK17 may be considered a promising candidate to use as a molecular marker for malignant transformation in laryngeal squamous cell carcinoma.
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2001
 
PMID 
I Doweck, K T Robbins, F Vieira (2001)  Analysis of risk factors predictive of distant failure after targeted chemoradiation for advanced head and neck cancer.   Arch Otolaryngol Head Neck Surg 127: 11. 1315-1318 Nov  
Abstract: BACKGROUND: Distant metastasis (DM) is the most common mode of recurrence among patients with advanced head and neck carcinoma treated with intra-arterial cisplatin and radiotherapy (RADPLAT). OBJECTIVE: To identify which patients are at greatest risk for DM and would benefit the most from new strategies designed to treat occult metastases. METHODS: Between 1993 and 1999, 250 patients with advanced head and neck cancer were treated by RADPLAT. Excluded from the analysis were 10 patients who either did not complete the protocol or were unavailable for follow-up and 39 patients with persistent disease or local recurrence. The incidence and the risk factors for DM in these patients were evaluated in a model that included the following factors: age, T and N classification, site of tumor, histologic grade, number (0, 1, or >1) and position (high vs low) of neck levels involved, and bilateral nodal disease. Multiple stepwise logistic regression was used for the analysis. RESULTS: In a univariate analysis, the following variables correlated to DM: N classification (P =.02), site of tumor (P =.01), lower neck nodes (P =.002), number of neck levels involved (P =.001), and bilateral nodal disease (P =.02). In a multivariate analysis, the most significant risk factors for DM were the number of neck levels involved and the site of the primary tumor (P<.001). The highest odds ratios for DM were among patients with multiple levels of nodal involvement (3.17) and patients with hypopharyngeal carcinoma (2.8). CONCLUSIONS: Patients with more than 1 level of clinical nodal involvement and patients with hypopharyngeal carcinoma have the highest risk of developing DM as the initial site of failure and would benefit most from treatment strategies that address occult distant disease.
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PMID 
C R Gordon, A Gonen, Z Nachum, I Doweck, O Spitzer, A Shupak (2001)  The effects of dimenhydrinate, cinnarizine and transdermal scopolamine on performance.   J Psychopharmacol 15: 3. 167-172 Sep  
Abstract: We assessed the influence of dimenhydrinate, cinnarizine and transdermal scopolamine on the ability to perform simulated naval crew tasks. The effect of single doses of dimenhydrinate, 100 mg, cinnarizine, 50 mg, and one transdermal scopolamine patch on psychomotor performance was evaluated using a double-blind, placebo-controlled, randomized, crossover design in three separate studies. A total of 60 young naval crew (20 for dimenhydrinate, 15 for cinnarizine and 25 for transdermal scopolamine) underwent a battery of computerized and paper and pencil performance tests, and filled out a questionnaire on side-effects and well-being self-assessment. Dimenhydrinate significantly impaired decision reaction time and auditory digit span. Most of the subjects who took dimenhydrinate also reported a subjective decrease in well-being and general performance abilities. Cinnarizine and transdermal scopolamine did not affect performance abilities. Cinnarizine was free of significant side-effects. Dry mouth was the only significant side-effect of transdermal scopolamine. These findings could be explained by the well-known sedative properties of dimenhydrinate and not by a specific effect on any particular cognitive or motor function. Our results suggest that dimenhydrinate, 100 mg, adversely affects psychomotor function, whereas single doses of cinnarizine, 50 mg, and transdermal scopolamine appear to be free of side-effects on performance and seem to be a preferable anti-seasickness drug for use by a naval crew.
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PMID 
Z Nachum, A Shupak, O Spitzer, Z Sharoni, I Doweck, C R Gordon (2001)  Inner ear decompression sickness in sport compressed-air diving.   Laryngoscope 111: 5. 851-856 May  
Abstract: OBJECTIVE: We report our experience over the past 12 years with recreational diving-related inner ear decompression sickness (IEDCS). STUDY DESIGN: Retrospective, consecutive case series. METHODS: Twenty-four divers, representing 29 cases of IEDCS, are presented with regard to evaluation, treatment, and follow-up. RESULTS: These 29 cases represent 26% of the severe decompression sickness (DCS) cases treated in that period. The patient group includes 22 divers who had a single event of IEDCS, one diver who had two events, and one with five repeated episodes. The cause of injury in 23 cases (79%) was violation of the decompression schedule. The mean time from surfacing to appearance of symptoms was 47 +/- 65 minutes. In 83%, symptoms appeared within 1 hour of ascent, in 97% within 2 hours, and in only one diver after 5.5 hours. Ten divers (34%) had pure vestibular involvement, 4 (14%) had cochlear insult alone, and 15 (52%) had combined vestibulo-cochlear injury. Except for one patient who had central as well as peripheral vestibulo-cochlear DCS, all the remaining patients had end organ involvement only, as demonstrated by physical examination and laboratory test results. Fifteen (52%) had isolated IEDCS, whereas 14 had additional symptoms of DCS. Twenty-six cases were treated by hyperbaric oxygenation with supplementary daily hyperbaric sessions. Of the 25 cases with vestibular injury and the 19 with cochlear damage, only 7 (28%) and 6 (32%), respectively, made a full recovery, whereas the others remained with residual damage. Of the 17 treated within 6 hours of symptom appearance, 9 (53%) were cured, compared with one of the 9 treated later (P <.05). CONCLUSIONS: IEDCS related to compressed-air recreational diving is more common than previously thought, and might occur even when no decompression schedule violation took place. Prompt diagnosis leading to the early commencement of hyperbaric oxygen recompression therapy is the key to complete recovery of cochlear and vestibular function.
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2000
 
DOI   
PMID 
I Doweck, M Barak, N Uri, E Greenberg (2000)  The prognostic value of the tumour marker Cyfra 21-1 in carcinoma of head and neck and its role in early detection of recurrent disease.   Br J Cancer 83: 12. 1696-1701 Dec  
Abstract: This study examines a new tumour marker, Cyfra 21-1, as a prognostic marker in predicting the survival of H&N cancer patients, and its correlation with clinical outcome during prolonged follow up of these patients. The study included 67 patients with primary detection of carcinoma of H&N. The survival of these patients was evaluated in correlation with the disease stage and Cyfra 21-1 levels at initial diagnosis. 38 patients were followed clinically and with serial assays for at least 12 months, or until recurrence was diagnosed. Cyfra 21-1 levels were determined periodically, using an Elisa kit. Patients with Cyfra 21-1 < 1.5 ng ml(-1)had a higher survival rate compared to patients with Cyfra 21-1 > or = 1.5 ng ml(-1)(63% vs. 20%, respectively). The risk ratio of Ln(Cyfra 21-1) is 1.62 (P = 0.028). In a Cox regression model that included the disease stage and Ln(Cyfra 21-1), Ln(Cyfra 21-1) was preferred as the main parameter for predicting patients survival. In 83% of the 12 patients with recurrent or residual disease, Cyfra 21-1 was elevated before or during clinical detection of the recurrence. Cyfra 21-1 was found to be a prognostic marker for carcinoma of H&N, unrelated to the stage of the disease. Elevated levels of Cyfra 21-1 without clinical evidence of disease can be attributed to the marker's mean lead-time as compared to the clinical appearance of the disease.
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1997
 
PMID 
I Doweck, C R Gordon, A Shlitner, O Spitzer, A Gonen, O Binah, Y Melamed, A Shupak (1997)  Alterations in R-R variability associated with experimental motion sickness.   J Auton Nerv Syst 67: 1-2. 31-37 Dec  
Abstract: Motion sickness is a complex integration of responses from multiple physiological systems. Whether the changes that occur during the time course of motion sickness are mediated by the sympathetic or parasympathetic systems is still controversial. The present study evaluates alterations in R-R variability during experimental motion sickness in motion sick and non-motion sick subjects. Ten motion sick subjects and 7 non-motion sick subjects participated in the study. Power spectrum analysis of R-R variation was conducted for all subjects 10 min before a brief vestibular disorientation test (BVDT), for 5-10 min of the test, and 10 min after the test. Subjects were also asked to report their symptoms during the test. The motion sick group showed a significant reduction in the power spectrum density of the R-R interval at the mid and high frequencies during the BVDT test period (BVDT), in comparison with the rest period (Rest). These changes probably indicate a decrease in parasympathetic activity during the time course of motion sickness. The non-motion sick group did not show significant differences at any of the frequencies during BVDT. Power spectrum analysis of the R-R interval provides an objective measure of the autonomic response to experimental motion sickness.
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1996
 
PMID 
C R Gordon, O Spitzer, I Doweck, A Shupak, N Gadoth (1996)  The vestibulo-ocular reflex and seasickness susceptibility.   J Vestib Res 6: 4. 229-233 Jul/Aug  
Abstract: VOR parameters were compared in subjects at the extremes of the seasickness susceptibility scale. Thirty-nine subjects highly susceptible to seasickness and 30 nonsusceptible subjects participated in the study. The VOR was evaluated by the Sinusoidal Harmonic Acceleration (SHA) test at frequencies of 0.01, 0.02, 0.04, 0.08, and 0.16 Hz. In subjects susceptible to seasickness, VOR gain was significantly higher at 0.02 and 0.04 Hz, and phase lead was significantly lower at 0.01, 0.02, 0.04, and 0.08 Hz, than in nonsusceptible subjects. Our findings are in agreement with the notion that the vestibular response will be more intense in subjects susceptible to motion sickness. The present results support the contention that a natural insusceptibility, or increased resistance to seasickness produced by adaptive responses to repeated sea exposures, may be reflected by lower VOR gain and higher phase lead.
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PMID 
C R Gordon, A Shupak, O Spitzer, I Doweck, Y Melamed (1996)  Nonspecific vertigo with normal otoneurological examination. The role of vestibular laboratory tests.   J Laryngol Otol 110: 12. 1133-1137 Dec  
Abstract: Vestibular laboratory tests are not generally necessary in the diagnosis of patients with a clear description of vertigo accompanied by positive otoneurological examination findings. The purpose of the study was to investigate the role of conventional vestibular laboratory tests in the diagnosis of patients complaining of nonspecific vertigo, despite their having a documented normal otoneurological examination. The results of the standard electronystagmography (ENG) and sinusoidal harmonic acceleration (SHA) tests of 52 patients referred for ambulatory vestibular laboratory tests due to a nonspecific illusion of movement, but with a normal otoneurological examination, were reviewed. Abnormalities were found in the vestibular tests of 35 patients (67 per cent), 22 of whom (63 per cent) were finally diagnosed as having a unilateral peripheral vestibular lesion, and 13 (37 per cent) benign positional vertigo. These results suggest that a high percentage of patients with nonspecific vertigo and a normal otoneurological examination probably suffer from peripheral vestibular dysfunction, which can be objectively documented by the ENG and SHA tests.
Notes:
1995
 
PMID 
I Doweck, M Barak, E Greenberg, N Uri, J Kellner, M Lurie, N Gruener (1995)  Cyfra 21-1. A new potential tumor marker for squamous cell carcinoma of head and neck.   Arch Otolaryngol Head Neck Surg 121: 2. 177-181 Feb  
Abstract: OBJECTIVE: Evaluation of Cyfra 21-1 (cytokeratin fraction 21-1) in squamous cell carcinoma of the head and neck. DESIGN: Prospective study. PATIENTS: Serum Cyfra 21-1 concentration was measured in 250 samples from patients with squamous cell carcinoma of head and neck, patients with benign tumors of head and neck, healthy control subjects, and patients in remission from squamous cell carcinoma of head and neck. RESULTS: Cyfra 21-1 concentration was elevated in 60% of the new patients with squamous cell carcinoma but only in 8% of patients with benign tumors and 3.5% of the healthy controls. At a cutoff of 1.3 ng/mL, the sensitivity of the test was 60%, the specificity was 94%, positive predictive value was 75%, and negative predictive value was 89%. The marker levels tended to follow the clinical course of the disease and were useful for therapy monitoring. Cyfra 21-1 levels were in good correlation with the tumor stage expressed by the local (T) and the lymphatic spread (N) and were inversely correlated with histologic grade, eg, higher in poorly differentiated carcinoma than in well-differentiated squamous cell carcinoma. CONCLUSION: Cyfra 21-1 evaluation in head and neck squamous cell carcinoma is worthwhile for performance of an ample study that will prove and establish its routine use.
Notes:
 
PMID 
C R Gordon, O Spitzer, I Doweck, Y Melamed, A Shupak (1995)  Clinical features of mal de debarquement: adaptation and habituation to sea conditions.   J Vestib Res 5: 5. 363-369 Sep/Oct  
Abstract: A survey conducted among 116 crew members of seagoing vessels confirmed that mal de debarquement (M-D) is a transient feeling of swinging, swaying, unsteadiness, and disequilibrium. None of the subjects requested medical attention, although there were isolated cases in which a strong sensation of swinging and unsteadiness caused transient postural instability and impaired the ability to drive. In most cases, the sensation of M-D appeared immediately on disembarking and generally lasted a few hours. In addition, subjects usually described bouts or attacks of M-D associated with changes in body posture, head position, or with closing of the eyes. M-D was reported by 72% of our subjects. Sixty-six percent of subjects reported a high incidence following their first voyages. A significant positive correlation was found between M-D and seasickness susceptibility. The nature of M-D may be explained within the framework of multisensorimotor adaptation and habituation to a new or abnormal motion environment. It is suggested that M-D represents a dynamic, multisensorimotor form of CNS adaptive plasticity.
Notes:
1994
 
PMID 
I Doweck, C R Gordon, O Spitzer, Y Melamed, A Shupak (1994)  The vestibulo-ocular reflex (VOR) under the influence of cinnarizine.   J Vestib Res 4: 3. 215-220 May/Jun  
Abstract: In a double-blind, placebo controlled, crossover study, we evaluated the effects of cinnarizine on the VOR of 55 healthy young subjects. VOR was evaluated by the Sinusoidal Harmonic Acceleration (SHA) test at frequencies of 0.01, 0.02, 0.04, 0.08 and 0.16 Hz. There was a reduction in VOR gain in 16 of the 20 SHA trials performed under the influence of cinnarizine alone (25 mg and 50 mg) and cinnarizine 25 mg in combination with 10 mg domperidone or 1 transdermal scopolamine patch. This decrease in VOR gain was significant in only a few SHA trials. Phase lead was not consistently affected by cinnarizine. No notable side effects were found for any of the drug groups. Our findings are in accord with the contention that increased resistance to seasickness produced either by drugs, or by the natural process of habituation to sea conditions, may be reflected by a decrease in VOR gain.
Notes:
 
PMID 
A Shupak, I Doweck, C R Gordon, O Spitzer (1994)  Cinnarizine in the prophylaxis of seasickness: laboratory vestibular evaluation and sea study.   Clin Pharmacol Ther 55: 6. 670-680 Jun  
Abstract: Cinnarizine was evaluated for the prevention of seasickness in a laboratory and sea study. The effects of 25 mg cinnarizine on the vestibulo-ocular reflex were investigated in 13 subjects. Significant reduction of the gain in response to sinusoidal oscillations at 0.02, 0.08, and 0.16 Hz (p < 0.05) and increased phase lead at 0.16 Hz (p < 0.01) were observed. The effect of 25 and 50 mg cinnarizine on seasickness severity was examined in 95 subjects during a voyage in rough seas. Seasickness symptoms were improved in 69% of the subjects by 50 mg cinnarizine versus 35% and 31% in the groups receiving 25 mg cinnarizine and placebo (p < 0.05 and p < 0.01, respectively). The percentage of vomiting protection provided by 50 mg cinnarizine was 63% (p < 0.05). We conclude that 50 mg cinnarizine is an effective drug for the prevention of seasickness. The reduction in vestibular sensitivity observed even after administration of 25 mg cinnarizine may explain the potency of cinnarizine in the prevention of seasickness.
Notes:
 
PMID 
I Doweck, C R Gordon, O Spitzer, Y Melamed, A Shupak (1994)  Effect of cinnarizine in the prevention of seasickness.   Aviat Space Environ Med 65: 7. 606-609 Jul  
Abstract: In a double-blind, placebo-controlled study, we evaluated the effect of two different doses of cinnarizine in the prevention of seasickness in very rough seas. We divided 95 healthy male subjects into 3 groups which received: cinnarizine 50 mg, cinnarizine 25 mg, and placebo. Seasickness susceptibility and severity were evaluated by a standard questionnaire concerning the subject's condition on previous voyages (seasickness susceptibility), and the subject's condition immediately after a 4-6-h voyage in very rough seas with 3.5 m waves (seasickness severity). Possible side effects of the drug were also evaluated by filling in a further questionnaire. Of the 31 subjects who received cinnarizine 50 mg, 65% felt better during the present voyage than on previous voyages, compared to 41% of the 32 subjects who received cinnarizine 25 mg and 31% of the 32 who received placebo. A significant difference (p < 0.05) was found between the cinnarizine 50 mg and placebo groups, while cinnarizine 25 mg was no more effective than placebo. No notable side effects were found for any drug group. In conclusion, cinnarizine 50 mg was found to be effective in the prevention of seasickness in rough seas.
Notes:
 
PMID 
C R Gordon, H Ben-Aryeh, O Spitzer, I Doweck, A Gonen, Y Melamed, A Shupak (1994)  Seasickness susceptibility, personality factors, and salivation.   Aviat Space Environ Med 65: 7. 610-614 Jul  
Abstract: The present study investigates the possible relationship between motion sickness susceptibility, personality factors and salivation. Personality factors, as evaluated by the Eysenck Personality Questionnaire, and salivary composition and flow were measured in a group of 29 subjects highly susceptible to seasickness and in a group of 25 non-susceptible subjects. The non-susceptible group had significantly higher psychoticism scores and significantly lower salivary amylase levels compared to the highly susceptible group. A significant positive correlation was found between psychoticism scores and the amount of the increase in salivary flow in response to gustatory stimulation. These results provide more data in support of a connection between motion sickness susceptibility, personality, and the autonomic nervous system.
Notes:
1993
 
PMID 
C R Gordon, A Kuritzky, I Doweck, O Spitzer, A Shupak, R Hering (1993)  Vestibulo-ocular reflex in migraine patients: the effect of sodium valproate.   Headache 33: 3. 129-132 Mar  
Abstract: We studied vestibulo-ocular reflex measurements in a group of 12 patients suffering from migraine without aura and evaluated the effect of sodium valproate given as prophylactic migraine therapy. The study was randomized, double blind and placebo controlled, with a crossover design. The horizontal vestibulo-ocular reflex was evaluated by the Sinusoidal Harmonic Acceleration test at 0.01, 0.02, 0.04, 0.08 and 0.16 Hz using a computerized rotatory chair system. No abnormalities were found for the vestibulo-ocular reflex gain, phase and asymmetry at each of the frequencies examined during the placebo treatment. These normal vestibulo-ocular reflex measurements contrasted with the repeated complaints of dizziness, vertigo and unsteadiness reported by 7 patients (58%). Sodium valproate affected neither vestibulo-ocular responses nor vestibular complaints but was effective in reducing migraine attacks in 8 of the 12 patients. These results demonstrate that the low frequency vestibulo-ocular reflex measurements are normal in patients suffering from migraine without aura.
Notes:
1992
 
PMID 
C R Gordon, Y Jackman, H Ben-Aryeh, I Doweck, O Spitzer, R Szargel, A Shupak (1992)  Salivary secretion and seasickness susceptibility.   Aviat Space Environ Med 63: 5. 356-359 May  
Abstract: The salivary flow rate and composition of 2 groups of 31 subjects, one group at each extreme of the seasickness susceptibility scale, were compared. No significant differences were found between the two groups in flow rates and electrolyte concentrations of whole resting and stimulated saliva. Amylase activity and rate of secretion in resting saliva were significantly higher in subjects susceptible to seasickness as compared with nonsusceptible subjects. Also, the total protein rate of secretion in resting saliva was significantly higher in the susceptible group. The present findings could be explained in terms of higher sympathetic tone in subjects susceptible to seasickness, and salivary amylase levels might be recommended as an additional parameter in the evaluation of seasickness susceptibility.
Notes:
1991
 
PMID 
C R Gordon, D Mankuta, A Shupak, O Spitzer, I Doweck (1991)  Recurrent classic migraine attacks following transdermal scopolamine intoxication.   Headache 31: 3. 172-174 Mar  
Abstract: A 20 year old male naval crew-member suffering from sea sickness was treated with transdermal scopolamine (TS). After 5 months of continuous treatment, he developed scopolamine intoxication followed by the appearance of recurrent classic migraine attacks. He had never suffered from headache or migraine prior to TS intoxication. The migraine attacks comprised a prodrome of apathy, bad mood and loss of appetite lasting several hours. An aura of scintillating spots, left arm numbness and paresthesias lasting several minutes was followed by a severe throbbing unilateral headache with photophobia, sonophobia and nausea. After one year of repeated follow-up examination, he continued to suffer from the attacks once every 10 to 14 days, with no identified precipitating factors. We are not aware of similar cases in the medical literature. Although it is not possible to establish TS intoxication as a causal effect of the appearance of classic migraine in our patient, the temporal association and clinical course are very supportive of this assumption. Central nervous system neurotransmitter imbalance of cardiovascular alterations may possibly be implicated.
Notes:
 
PMID 
A Shupak, Z Sharoni, E Ostfeld, I Doweck (1991)  Pressure chamber tympanometry in diving candidates.   Ann Otol Rhinol Laryngol 100: 8. 658-660 Aug  
Abstract: The currently recommended examination for diving fitness ascertains middle ear autoinflation ability only under surface pressure conditions. The purpose of our study was to document and quantify middle ear pressure equalization failure during simulated dives among diving candidates who had otherwise met the otologic criteria for diving fitness. Forty-two candidates for regular naval diving activity were included in the study. Tympanograms of both ears at 1 and 1.1 absolute atmospheres (ATA) were taken inside a pressure chamber with the subjects in two positions: seated and supine. At a pressure of 1 ATA, type A tympanograms were found in all 84 ears examined. At a pressure of 1.1 ATA, with subjects in the upright position, 19 (22.9%) of the ears had type C and 2 (2.4%) type B tympanograms, while with subjects recumbent during descent, 6 of the ears (7.2%) had type C and 7 (8.4%) type B. Our results suggest that successful autoinflation at surface ambient pressure does not necessarily reflect middle ear pressure equalization ability during descent in a dive.
Notes:
 
PMID 
A Shupak, I Doweck, E Greenberg, C R Gordon, O Spitzer, Y Melamed, W S Meyer (1991)  Diving-related inner ear injuries.   Laryngoscope 101: 2. 173-179 Feb  
Abstract: Diving-related inner ear barotrauma (IEB) and inner ear decompression sickness (IEDS) most often result in permanent severe cochleovestibular deficits, unless immediate diagnosis is reached and the correct treatment is commenced early. Nine cases of sport-diving-induced inner ear injuries that were referred to the Israeli Naval Hyperbaric Institute between October 1987 and September 1989 are presented with regard to evaluation, treatment, and follow-up. The diagnosis was IEB in five divers and IEDS in four. Explorative tympanotomy was carried out with remarkable results in two patients with IEB, while the remaining three were relieved by bed rest alone. Three of the four IEDS patients were recompressed according to the extended US Navy Table 6 with good short-term results. The role of complete otoneurological evaluation in the decision-making process leading to the correct diagnosis and treatment is emphasized.
Notes:
1989
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