bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Significance of Tenascin-C Splice Variant Expression in Chondrosarcoma
Authors: Ghert Michelle A. , Jung Sung Taek , Qi Wen-ning , Harrelson John M. , Erickson Harold P. , Block Joel A. , Scully Sean P.
Published: April 2003

Objectives: Tenascin-C (TNC) is an oligomeric glycoprotein of the extracellular matrix that is prominently expressed in malignant tumors. The purpose of this study was: (1) to determine the in vitro TNC splicing pattern in cultured human chondrocytes and chondrosarcoma cells, (2) to determine the in vivo TNC splicing pattern in clinical chondrosarcoma specimens, and (3) to perform survival analysis based on the TNC splicing pattern of the tumor specimens. Methods: Human articular chondrocytes and chondrosarcoma cells (cell line JJ012) were grown in a three-dimensional alginate bead system and harvested at two time points. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine the in vitro TNC splicing pattern for the two cell types. Clinical chondrosarcoma specimens were obtained intra-operatively and underwent RT-PCR to determine the in vivo TNC splicing pattern. Specific immunohistochemical staining for the large TNC splice variant was performed on the clinical specimens. Survival analysis was used to determine the association between the specific TNC splicing pattern and survival. Results: The in vitro mRNA expression pattern of TNC in normal human articular chondrocytes was characterized by a high ratio of the small to the large splice variant (TNCsmall:TNClarge), whereas the in vitro mRNA expression pattern for cultured chondrosarcoma cells was characterized by a low TNCsmall:TNClarge ratio. Clinical chondrosarcoma specimens with a lower TNCsmall:TNClarge ratio showed a trend towards decreased survival. The TNC splicing pattern of these specimens was verified through specific immunohistochemical staining for the large TNC isoform. Conclusions: The specific TNC splicing pattern may have clinical significance in chondrosarcoma. TNC expression may therefore play a future role in objecitve tumor grading and novel therapeutic approaches to this malignancy.
Oxaliplatin in Combination with Infusional 5-Fluorouracil and Leucovorin Every 2 Weeks as First-Line Treatment in Patients with Advanced Colorectal Cancer: A Phase II Study
Authors: Kouroussis Ch. , Souglakos J. , Kakolyris S. , Mavroudis D. , Malamos N. , Kalbakis K. , Androulakis N. , Agelaki A. , Vardakis N. , Samonis G. , Georgoulias V.
Published: April 2003

Purpose: To evaluate the efficacy and safety of oxaliplatin (L-OHP) in combination with leucovorin (LV)-modulated bolus plus infusional 5-fluorouracil (5-FU; de Gramont schedule) every 2 weeks in chemotherapy-naive patients with advanced colorectal cancer (CRC). Patients and Methods: Thirty-two patients (median age: 69 years) with histologically confirmed and two-dimensionally measurable metastatic CRC were enrolled. The patients’ performance status (WHO) was 0 in 14 (44%), 1 in 15 (47%), and 2 in 3 (9%) patients. Twenty (62.5%) patients had at least two metastatic sites. LV was administered at a dose of 200 mg/m2/day as a 2-hour intravenous infusion, followed by 5-FU as an intravenous bolus at the dose of 400 mg/m2 and then, as a 22-hour continuous infusion at the dose of 600 mg/m2/day for 2 consecutive days. L-OHP was administered on day 1 at the dose of 85 mg/m2 as a 2-hour infusion in parallel with LV but using different infusion lines. Treatment was administered every 2 weeks. Results: In an intention-to-treat analysis, 2 (6.2%) complete and 9 (28%) partial responses (28%; odds ratio 34.2%; 95% confidence interval 17.92–50.83%) were achieved while 8 (25%) patients had stable disease and 13 (41%) progressive disease. The median duration of response was 5 months, but the median time to progression has not yet been reached. After a median follow-up period of 11 months, the median survival has not yet been attained, but the projected probability for 1-year survival was 72%. Grade 3/4 neutropenia occurred in 16 (50%) patients while 1 (3%) of them developed febrile neutropenia. There was no treatment-related death. Peripheral neuropathy grade 2 and ≧3 occurred in 5 (16%) and 7 (21%) patients, respectively. Conclusions: The bimonthly administration of L-OHP in association with LV-modulated bolus plus infusional 5-FU (‘de Gramont’ regimen) is a well-tolerated and effective front-line treatment for metastatic CRC.
A Literature Analysis of Prognostic Factors for Response and Quality of Response of Patients with Renal Cell Carcinoma to Interleukin-2-Based Therapy
Authors: Elias Laurence , Hunt William C.
Published: April 2003

Objective: To characterize prognostic factors for response of advanced renal cell carcinoma to interleukin-2-based regimens. Patients and Methods: Data compiled from 80 published series were examined for associations between patient characteristics and outcomes. Results: Response rates were highest in trials utilizing interleukin-2 combinations. Longer median survivals were associated with high percentages of patients with nephrectomy, good performance status, with publication year, response rates, and inversely with median ages. Associations of performance status and prior nephrectomy with response rates were detected in trials with individual patient details. The response rate was higher for patients older than the median age of patients entering each trial, and also higher for males. Among responders, attainment of complete response was associated with fewer sites of involvement. Pooled response duration of patients reported to have complete responses exhibited durability, but no correlation with prognostic factors. Selection factors may have influenced apparent differences between types of regimens. We confirm the potential for durable remissions from interleukin-2-based regimens.
A Phase I Study of Raltitrexed (Tomudex) Combined with Carmofur in Metastatic Colorectal Cancer
Authors: Österlund Pia , Elomaa Inkeri , Virkkunen Pekka , Joensuu Heikki
Published: April 2003

Objectives: The aim of the study was to define the maximum tolerated dose (MTD) of the combination of raltitrexed plus carmofur, and to evaluate the tolerability and efficacy of this combination in metastatic colorectal cancer. Methods: Twenty-eight patients (23 receiving first-line therapy, 5 receiving second-line therapy) entered the study; 16 were chemonaive. Raltitrexed (Tomudex) 1.5–3.0 mg/m2 was given as a 15- to 30-min intravenous infusion on day 1 of a 21-day cycle followed by carmofur 300–400 mg/m2 orally 3 times daily on days 2–14. Therapy was given until disease progression or dose-limiting toxicity (DLT) occurred. Results: A total of 170 cycles of therapy were administered. The MTD was reached at the raltitrexed dose of 3.0 mg/m2 and the carmofur dose of 400 mg/m2. DLTs included grade 3–4 diarrhea, fatigue, anorexia, mucositis, anemia, thrombocytopenia, neutropenia, neurological symptoms and febrile neutropenia. Eleven of the 22 evaluable first-line patients achieved a partial response (response rate 50%, 95% confidence interval 29–71%), 8 had stable disease and 3 had disease progression. One of the 5 patients who received second-line therapy responded. Conclusions: The recommended dose of this combination therapy for further evaluation is raltitrexed 3.0 mg/m2 plus carmofur 300 mg/m2. This combination has unique but manageable toxicity and promising efficacy in metastatic colorectal cancer.
Hypersensitivity Reactions to Carboplatin Administration Are Common but Not Always Severe: A 10-Year Experience
Authors: Polyzos Aristidis , Tsavaris Nicolas , Kosmas Christos , Arnaouti Theodora , Kalahanis Nicolas , Tsigris Christos , Giannopoulos Athanasios , Karatzas Gabriel , Giannikos Lambros , Sfikakis Petros P.
Published: April 2003

We have retrospectively evaluated and characterized the hypersensitivity reactions associated with carboplatin administration in ovarian cancer patients treated mainly on an outpatient basis at the Laikon Hospital from 1988 to 1998. A total of 240 patients, who had never been exposed to platinum compounds previously, received carboplatin plus cyclophosphamide (n = 58) or paclitaxel (n = 136) intravenously, and intraperitoneal carboplatin plus intravenous cyclophosphamide (n = 46). The median number of carboplatin courses was 6 (range 3–12) and 5 (range 4–6) for the intravenous and intraperitoneal treatment regimens, respectively. Thirty-two of 194 patients (16%) who were on intravenous carboplatin treatment developed symptoms compatible with a hypersensitivity reaction to carboplatin, that was always verified by manifestation of at least similar symptoms on rechallenging. In contrast, in the group of 46 patients on intraperitoneal carboplatin treatment, no hypersensitivity reaction was ever noticed. Hypersensitivity reactions always occurred after administration of the first 4 intravenous courses of carboplatin; 4, 19, 4, and 5 reactions occurred at the 5th, 6th, 7th, and 8th courses, respectively. These reactions could be distinguished in: (a) mild hypersensitivity reactions in 20 of 194 patients, which manifested as itching (20 patients) and small area erythema plus erythema of the palms and soles (12 patients), occurring either during intravenous injection when most of the drug scheduled had been administered, or within 3 days, and (b) in severe reactions in 12 of 194 patients, which manifested acutely as itching, diffuse erythroderma, rigor, facial swelling, throat and chest tightness, tachycardia (12 patients) and bronchospasm (2 patients), and hypertension or hypotension in 8 and 4 patients, respectively. With appropriate symptomatic management, discontinuation of carboplatin treatment was not required in patients with mild hypersensitivity reactions, but none of the 12 patients with severe reactions was able to receive a full subsequent dose of carboplatin on rechallenging. However, in 4 of these 12 patients carboplatin was replaced by cisplatin, which was given for 4–6 courses without side effects. These findings indicate that although hypersensitivity reactions are common in general, occurring in almost 1 of every 6 patients treated intravenously with carboplatin, their clinical picture is variable, leading to discontinuation of treatment in only 6% of patients. This is not the case when the intraperitoneal route of carboplatin administration is used when indicated.
Gastric and Intestinal Phenotypic Marker Expression in Gastric Carcinomas and Its Prognostic Significance: Immunohistochemical Analysis of 136 Lesions
Authors: Tajima Yusuke , Shimoda Tadakazu , Nakanishi Yukihiro , Yokoyama Noboru , Tanaka Takayuki , Shimizu Kouji , Saito Toyohiko , Kawamura Masatoshi , Kusano Mitsuo , Kumagai Kazuhide
Published: April 2003

Objective: It is well known that both gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. However, the clinicopathologic significance of these expressions has not yet been clarified. Methods: We analyzed the correlations among gastric and intestinal phenotypic marker expression patterns of the tumor, clinicopathologic findings and the patient’s outcome in 136 advanced gastric carcinomas. Results: Phenotypic marker expression was immunohistochemically evaluated using the monoclonal antibodies 45M1 (anti-human gastric mucin; HGM), CLH5 (anti-MUC6), Ccp58 (anti-MUC2) and 56C6 (anti-CD10). All tumors were classified as gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotype. Of the 136 gastric carcinomas, 50 (36.8%), 56 (41.2%), 21 (15.4%) and 9 (6.6%) were classified as G, GI, I and UC phenotype, respectively. The G-phenotype tumors were associated with a higher rate of undifferentiated-type and infiltrative histology as compared with the I-phenotype tumors (p < 0.05 and p < 0.001, respectively). Furthermore, both univariate and multivariate analysis of survival revealed the G-phenotype tumor to be associated with a significantly poorer outcome than the I-phenotype tumor (p < 0.05). Conclusion: Our present results indicate that the gastric and intestinal phenotypic marker expression pattern of tumors, determined by the combination of HGM, MUC6, MUC2 and CD10 expression, is prognostically useful for patients with gastric carcinoma.
New Advances in Lung Cancer Chemotherapy: Topotecan and the Role of Topoisomerase I Inhibitors
Authors: Huang Chao Hui , Treat Joseph
Published: April 2003

Objective tumor responses and survival rates with standard chemotherapy options for small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) have been disappointing. However, several promising new classes of agents have emerged in recent years, including the taxanes, mitotic spindle inhibitors, antimetabolites, and topoisomerase I and II inhibitors. The molecular target of several of these new agents is topoisomerase I, an enzyme that is essential for DNA replication and is up-regulated in tumor cells. Inhibition of this enzyme by drugs such as topotecan and irinotecan leads to cell death and is the basis for their anticancer activity. The process of DNA replication is halted by the covalent binding of the drug in a topoisomerase I drug/DNA ternary reaction intermediate. The pharmacokinetics of the approved regimen – a 30-min infusion daily for 5 days at 21-day intervals – are well defined, with proportional increases in the area under the plasma concentration-time curve, peak plasma concentration, and steady state concentration following application of higher doses. The antitumor activities of both the intravenous and oral formulations of topotecan have been tested in clinical trials. Topotecan is well tolerated and has demonstrated good efficacy in patients with relapsed SCLC when administered as monotherapy or in combination regimens as first-line or second-line therapy. Preliminary trials also indicate that topotecan is well tolerated and has activity in the first-line treatment of NSCLC. In this article an overview of new agents in lung cancer chemotherapy is provided, with particular attention paid to the topoisomerase I inhibitors. A review of topotecan – the first topoisomerase I inhibitor to be approved for second-line therapy in SCLC – is presented as an illustration of the promise these new agents hold for the treatment of SCLC and NSCLC.
Interaction between Herceptin® and Taxanes
Authors: Diéras Véronique , Beuzeboc P. , Laurence V. , Pierga J.Y. , Pouillart P.
Published: April 2003

The taxanes and Herceptin® have been shown to possess significant clinical activity in metastatic breast cancer. Preclinical testing of taxane/Herceptin combinations demonstrated additive and synergistic interactions with paclitaxel and docetaxel, respectively. In a pivotal clinical trial, combination of paclitaxel (3-weekly) and Herceptin was associated with an increased response rate compared with paclitaxel monotherapy (41% vs. 17%; p = 0.001). The combination therapy also significantly improved time to disease progression (6.9 vs. 2.7 months; p < 0.05). In a phase II study of weekly paclitaxel plus Herceptin in patients with normal or increased tumor HER2 levels, a response was observed in 60% of patients and the regimen was well tolerated. Responses were more frequent in patients with HER2-overexpressing tumors (83% vs. 45%). Preliminary results from a phase II study of Herceptin plus docetaxel in patients with HER2-overexpressing tumors indicate significant activity, with a response observed in 7 (44%) of 16 evaluable patients. The preliminary results of a trial of weekly docetaxel and Herceptin demonstrate a response rate of 54% in 13 evaluable patients. Additional European trials of Hercep- tin/taxane combinations as first- and second-line and adjuvant therapy are ongoing. The results of the studies to date indicate that regimens combining Herceptin with 3-weekly and weekly taxane are effective and well tolerated.
Melanoma of the Choroid above the Optic Disc: Considerations Concerning a Clinical Case
Authors: Bacchetti Sonia , Bressan Paolo , Della Mea Giovanni
Published: April 2003

The authors report the case of a patient suffering from melanoma of the choroid above the optic disc. Given the good level of visual acuity and the location and extent of the damage, he was given a radiotherapy treatment with proton beams. At an interval of 6 months from this treatment, the neoformation appeared limited, and no vascular changes due to irradiation were observed.
Copper, Lead, Cadmium and Calcium in Cataractous Lenses
Authors: Cekic Osman
Published: April 2003

Lenticular copper, lead, cadmium and calcium levels were measured using atomic absorption spectrophotometry in 9 normal and 37 cataractous human lenses. The nuclear parts of the lenses were used for the study in both groups. The lenticular deposition of these four elements in cataract was statistically significant. In the cataractous group, males had higher levels of cadmium compared to females. No lead was detected in normal lenses. The calcium content was significantly higher in cortical cataract whereas the other elements were not correlated with the types of cataract.
Altered Organization of Collagen in the Apex of Keratoconus Corneas
Authors: Radner W. , Zehetmayer M. , Skorpik Ch. , Mallinger R.
Published: April 2003

Purpose: In 15 keratoconus corneas, the three-dimensional arrangement of collagen lamellae was investigated by means of scanning electron microscopy. Methods: Keratoconus corneas without visible scars were obtained during perforating keratoplasty. The noncollagenous matrix of the stroma was removed with sodium hydroxide. Descemet’s membrane was removed mechanically and deeper layers of the stroma were exposed by cutting the tissue tangentially to the corneal surface with an ultramicrotome. The apical and the para-apical regions of keratoconus were compared to the central regions of normal corneas. Results: In the apical regions of 11 out of the 15 keratoconus corneas (73%), the arrangement of the collagen lamellae differs from those of the para-apical regions and normal corneas. Their collagen fibrils form uniform layers and no delimited collagen lamellae can be differentiated. Interlacing between adjacent layers is extremely decreased or even absent. In the para-apical region of keratoconus corneas the three-dimensional arrangement of collagen lamellae does not differ from that in normal corneas. Conclusion: Stromal thinning and conical ectasia in the apex of keratoconus corneas alters the organization of collagen. This will certainly affect the biomechanical properties of the cornea and further lead to a progression of keratoconus irrespective of its primary pathogenesis.
The Relationship between Rabbit Corneal Opacity and Immunohistochemical Expression of Heat Shock Protein 72/73 and c-fos after Excimer Laser Photorefractive Keratectomy
Authors: Hong Jong Wook , Lee Tae Soo
Published: April 2003

To evaluate the etiology of corneal opacities, a study was done on the immunohistochemical staining for heat shock protein (HSP) 72/73 and c-fos after myopic excimer laser photorefractive keratectomy (PRK). New Zealand white rabbits (60 eyes) were divided into four groups: –6-, –9- and –15-dpt operation groups and a control group (only corneal epithelium removed). Using an excimer laser (VisX 20/20, Sunnyvale, Calif., USA), myopic PRK was performed on the rabbit’s cornea by a single or multizone technique followed by an immunohistochemical stain to detect the expression of HSP 72/73 and c-fos at 6, 24, 48 h, 1 week and 8 weeks. Corneal epithelia were healed within 3 days in all groups, and 8 weeks after the operation, the mean density of corneal opacity was 0.83 (–6-dpt operation group), 1 (–9-dpt operation group) and 1.67 (–15-dpt operation group). All groups exhibited HSP 73 in corneal epithelium and stroma. However, the maximal expression of c-fos and HSP 72 appeared in corneal epithelium at 24 and 48 h, respectively, after the operation in the –15-dpt group. These results suggest that the expressions of HSP 72 and c-fos in rabbit corneal epithelium are significant factors in relation to corneal opacity after excimer laser PRK.
Three-Dimensional Arrangement of Collagen Fibrils in Human Ciliary Body
Authors: Wang You-Dong , Chen Hai-Bo , Jin Ming , Ou Bo , Kashiwagi Kenji , Tsukahara Shigeo
Published: April 2003

The purpose of this study is to visualize the three-dimensional arrangement of collagen fibrils in aged human ciliary body and discuss their significance. The ciliary bodies obtained from two human eyes were treated with a NaOH cell-maceration method for 7 days, then prepared conventionally for light and scanning electron microscopy. The general morphology of the collagen tissue in the ciliary body appeared almost the same as that normally observed. Cellular elements were completely removed, but collagen fibrils were well preserved. In the stroma of the ciliary body, collagen fibrils were arranged irregularly. In the areas of the radial and circular ciliary muscles, considerable numbers of collagen fiber bundles were observed running in a circular direction. A honeycomb structure was seen in the pars plana, the walls and base of which were formed by interweaving collagen fibrils. The results suggested that collagen fibrils in the aged human ciliary body may be largely involved in the presbyopia.
Comparison of the Effects of Preserved and Unpreserved Formulations of Timolol on the Ocular Surface of Albino Rabbits
Authors: Pisella Pierre-Jean , Fillacier Kathleen , Elena Pierre-Paul , Debbasch Caroline , Baudouin Christophe
Published: April 2003

Thirty-six albino rabbits, randomly divided into six groups, were used to study their ocular tolerance to (a) 0.25 and 0.50% Timoptol® preserved with 0.01% benzalkonium chloride, (b) 0.25 and 0.50% Timoptol-LP®, a gel-forming solution preserved with 0.012% benzododecinium bromide, and (c) 0.25 and 0.50% Timabak® unpreserved in the ABAK® eyedrops dispenser. All eyedrops were applied in the right eye for 60 days. A clinical follow-up with slitlamp examination and break-up time evaluation was performed for 2 months. At the end of the experimentation, the animals were sacrificed and their eyes enucleated for histological analyses of the conjunctiva and cornea. There was no significant difference in the clinical examination between each group, except for the break-up time evaluation between Timoptol and Timabak at each concentration which was better with the unpreserved timolol. Histological results showed a significant difference in the corneal stroma edema between preserved and unpreserved timolol. This study confirms that using unpreserved timolol may be beneficial for the long-term treatment of glaucomatous patients as it increases tear film stability and decreases epithelial permeability and stromal aggression of the cornea.
Aqueous Dynamics in Experimental ab externo Trabeculectomy
Authors: Rossier Alain , Uffer Sylvie , Mermoud André
Published: April 2003

Purpose: This study assessed the decrease in intraocular pressure (IOP), the residual outflow resistance of the trabeculum and the filtration site by histology in enucleated pig and human eyes after ab externo trabeculectomy. Method: Measurement of the resistance to aqueous outflow was performed using the constant pressure method before and after ab externo trabeculectomy. Results: The outflow facility was 0.31 ± 0.13 µl/min/mm Hg in pig eyes and 0.24 ± 0.08 µl/min/mm Hg in human eyes before surgery, and 79.0 ± 47.6 µl/min/mm Hg in pig eyes and 6.33 ± 6.67 µl/min/mm Hg in human eyes after ab externo trabeculectomy. On histological examinations the aqueous outflow pathway was seen to be at the level of the residual trabecular meshwork. Conclusion: This study showed that ab externo trabeculectomy significantly lowers IOP and improves outflow facility in enucleated pig and human eyes.
Evaluation of the Norrie Disease Gene in a Family with Incontinentia pigmenti
Authors: Shastry Barkur S. , Trese Michael T.
Published: April 2003

Incontinentia pigmenti (IP) is an ectodermal multisystem disorder which can affect dental, ocular, cardiac and neurologic structures. The ocular changes of IP can have a very similar appearance to the retinal detachment of X-linked familial exudative vitreoretinopathy, which has been shown to be caused by the mutations in the Norrie disease gene. Therefore, it is of interest to determine whether similar mutations in the gene can account for the retinal pathology in patients with IP. To test our hypothesis, we have analyzed the entire Norrie disease gene for a family with IP, by single strand conformational polymorphism followed by DNA sequencing. The sequencing data revealed no disease-specific sequence alterations. These data suggest that ocular findings of IP are perhaps associated with different genes and there is no direct relationship between the genotype and phenotype.
No Increased Serum Levels of Antifood Antibodies in Patients with Ménière’s Disease
Authors: Boulassel Med-Rachid , Alost Marianne , Tomasi Jean-Paul , Deggouj Naima , Gersdorff Michel
Published: April 2003

The etiology of Ménière’s disease (MD) is still unknown, but it is likely to be multifactorial, one of the factors being an immunological causation. Antifood allergens as well as anti-baker’s yeast antibodies are humoral factors that may be linked with allergenic disorders and other autoimmune conditions. To determine their possible role in MD activity, we investigated 29 MD sera for the presence of antibodies against gliadin, β-lactoglobulin, albumin, ovalbumin, soya, and Dermatophagoides pteronyssinus and Saccharomyces cerevisiae strains using an ELISA technique. The patients were compared with 29 healthy individuals matched for sex and age. A serum was regarded as positive if the absorbance was two standard deviations higher than values obtained with sera from healthy subjects. Historical data, including factors which the patients believed to provoke their Ménière’s symptoms, were obtained from patients’ questionnaires. MD patients showed no significant symptoms of allergenic disorders suggesting allergies when compared to controls (p > 0.05). IgG and IgA antibody levels were not significantly raised in MD patients as compared with healthy controls (p > 0.05) for gliadin, β-lactoglobulin, soya, albumin, ovalbumin, and D. pteronyssinus and S. cerevisiae strains. These data do not convincingly support a hypothesis of increased serum levels of antifood antibodies in patients with MD, as very few patients were antibody positive.
Left Vocal Cord Paralysis in Cases of Systemic Lupus erythematosus
Authors: Imauchi Yutaka , Urata Yukitomo , Abe Kazuya
Published: April 2003

Two cases, a 41-year-old female and a 53-year-old female presenting with systemic lupus erythematosus and left vocal cord paralysis, are described in this paper. In both cases, laryngeal lupus and pulmonary hypertension were not detected. The laryngeal symptoms and signs were not improved by treatment with steroids, despite the systemic lupus erythematosus being under control.
Decreased Trigeminal Sensitivity in Anosmia
Authors: Gudziol Hilmar , Schubert Michael , Hummel Thomas
Published: April 2003

The present study aimed to investigate intranasal trigeminal sensitivity in a large sample of patients with anosmia due to different etiologies. We investigated the trigeminal detection threshold for formic acid in healthy controls (n = 96) and patients with anosmia due to head trauma (n = 18) or sinonasal disease (n = 54). Anosmics exhibited higher thresholds compared with normosmics (p < 0.001). In addition, thresholds were found to be higher in patients with posttraumatic anosmia compared to anosmics with sinonasal disease (p < 0.001). The data indicate that (1) loss of olfactory sensitivity in humans may be associated with a decreased sensitivity towards trigeminal stimuli and (2) alteration of intranasal trigeminal function is stronger in patients with posttraumatic anosmia compared to patients with sinonasal disease. This may have implications for the medicolegal investigation of anosmic patients where trigeminal stimuli are frequently used to assess the patient’s response bias.
Vasomotor Rhinitis: Clinical Efficacy of Azelastine Nasal Spray in Comparison with Placebo
Authors: Gehanno P. , Deschamps E. , Garay E. , Baehre M. , Garay R.P.
Published: April 2003

The H1 antagonist azelastine is used in nasal sprays for the treatment of allergic rhinitis, but its therapeutic efficacy in vasomotor rhinitis is unknown. We performed a multicenter randomized double-blind placebo-controlled study of the efficacy and tolerance of azelastine nasal spray in 89 adult patients with vasomotor rhinitis (confirmed by negative Phadiatop). Following a washout period, patients were treated for 15 days with one puff three times daily per nostril of azelastine (n = 44) or placebo (n = 45) nasal spray. Efficacy was evaluated by the reduction in symptomatology and by rhinoscopy. Intent-to-treat analysis revealed better results in the azelastine group for all assessed symptoms; the significance level was reached for nasal obstruction on day 15 (p = 0.042). Using per protocol analysis (in 85 patients complying with the protocol), the significance level was reached for nasal obstruction on day 15 (p = 0.017) and for the percentage of success in rhinorrhea (p = 0.023). In the azelastine group, rhinoscopy examination showed a significantly higher reduction in the inflammatory level and edema of the nasal mucosa (p = 0.03 and 0.02 for VAS on day 15 respectively, per protocol analysis). General efficacy assessment by the physician and the patient was in favor of azelastine (with significance levels <0.01). No drowsiness or serious adverse event was reported, and the frequency of mouth dryness and headaches was similar in the two treatment groups. The present study demonstrates the efficacy of azelastine nasal spray in the treatment of vasomotor rhinitis. The best achieved results were a decrease in nasal obstruction and mucosal edema. Further studies are required to investigate if this therapeutic benefit results from H1 antagonism or from another, not well-characterized pharmacological action of azelastine.
Genotoxicity of Nitroso Compounds and Sodium Dichromate in a Model Combining Organ Cultures of Human Nasal Epithelia and the Comet Assay
Authors: Kleinsasser Norbert H. , Gamarra Fernando , Bergner Albrecht , Wallner Barbara C. , Harréus Ulrich A. , Juchhoff Jutta , Kastenbauer Ernst R. , Huber Rudolf M.
Published: April 2003

Genotoxic effects of xenobiotics are a possible step in tumor initiation in the mucosa of the upper aerodigestive tract. Using the comet assay, detecting genotoxicity in human tissue has been restricted to single incubations in vitro, but in vivo most xenobiotics harm their target in a repetitive or chronic manner. Therefore, we propose a model, which provides repetitive incubations in human upper aerodigestive tract mucosa cultures. Samples of human inferior nasal turbinate mucosa (n = 25) were cultured according to a modified version of a technique originally described by Steinsvåg. On day 1 fresh samples and on days 7, 9 and 11 organ cultures were incubated with N-nitrosodiethylamine (NDEA), sodium dichromate (Na2Cr2O7) and N′-methyl-N-nitro-N-nitrosoguanidine (MNNG). Mucosa samples and organ cultures, respectively, underwent a modified comet assay on days 1, 7 and 11. Genotoxicity could be shown for NDEA, Na2Cr2O7 and MNNG on days 1, 7 and 11. Duration of tissue culture and repetitive incubations did not significantly influence the results for NDEA. Nevertheless, Na2Cr2O7 and MNNG caused higher genotoxic effects on cultures subjected to the comet assay on day 11. This model may help to assess genotoxic hazards posed by environmental pollutants that have a cumulative character in repetitive or chronic exposure in vivo.
Mastoid Condition and Clinical Course of Cholesteatoma
Authors: Hasebe Seishi , Takahashi Haruo , Honjo Iwao , Miura Makoto , Tanabe Makito
Published: April 2003

This study was carried out to establish which type of cholesteatoma is controllable by conservative treatment from the viewpoint of mastoid ventilation. We examined the area of the air cell system and airspace (aeration) in the mastoid cavity by computed tomography and eustachian tube (ET) function by inflation-deflation test in 20 ears (20 patients) with severe attic retraction for over 12 months (retraction pocket group), 16 ears (16 patients) with cholesteatoma which could be controlled only by conservative treatment for over 12 months (nonsurgical group) and 43 ears (43 patients) which required surgery within a year in spite of similar conservative treatment (surgical group). The size of the mastoid air cell system in the retraction pocket group, nonsurgical group and surgical group was 2.9 ± 1.3, 1.9 ± 0.7 and 1.5 ± 0.9 cm2 on average, respectively, with no significant difference between both cholesteatoma groups (nonsurgical and surgical group). While aeration was observed in the mastoid in 17 of 20 ears (85.%) in the retraction pocket group and in 12 of 16 ears (75.0%) in the nonsurgical group, aeration was present only in 9 of 43 ears (26.5%) in the surgical group, being significantly less in the surgical group than in the nonsurgical group and the retraction pocket group. In all ears in the retraction pocket and nonsurgical groups, and 19 of 30 ears in the surgical group, ET function was poor, there being no significant difference among the three groups. The present clinical observations suggest that progressiveness of cholesteatoma could be related to the ventilatory conditions in the mastoid rather than ET function, and that conservative treatment may be effective when ears with cholesteatoma have aeration in the mastoid.
Distant Metastases from Thyroid and Parathyroid Cancer
Authors: Shaha Ashok R. , Ferlito Alfio , Rinaldo Alessandra
Published: April 2003

Thyroid cancer represents a unique biological tumor where even with the high incidence of distant metastases, the overall prognosis is not as poor as many other human cancers. The overall long-term survival in patients presenting initially with distant metastasis is approximately 50%. The overall incidence of distant metastases varies between 10 and 35%, depending upon the histology. The overall incidence is directly related to various histologies – being least in papillary thyroid carcinoma (10%) and highest in Hürthle cell tumor (33%). The incidence of distant metastases is also very high in patients with medullary and anaplastic thyroid cancer. The incidence of distant metastases at the time of initial presentation in differentiated thyroid cancer is approximately 4%. In high-risk patients – especially in patients with extrathyroidal extension or massive nodal metastasis – the distant metastases can be evaluated after total thyroidectomy with radioactive iodine ablation. Pulmonary metastases are very common in young individuals, but they are extremely well treated and the mortality from distant metastases in this group is very low. However, distant metastases in patients with poorly-differentiated carcinoma have a poor prognosis. In high-risk patients, generally a total thyroidectomy should be undertaken so that the patient can undergo radioactive iodine dosimetry and ablation as indicated. The surveillance in patients with thyroid cancer includes: close clinical follow-up, chest X-ray, and radioactive iodine dosimetry. Thyroglobulin is commonly used as a prognostic marker in patients having undergone total thyroidectomy. The incidence of distant metastases in medullary thyroid cancer is high, mainly to the lung and liver. Persistent hypercalcitonemia is an indication of regional or distant metastases. A variety of diagnostic tests are helpful, such as octreotide scanning, computed tomography scan, magnetic resonance imaging and positron emission tomography scan. Laparoscopy to evaluate the surface of the liver is also an important investigation to detect distant metastases. The incidence of distant metastases is very high in patients with anaplastic thyroid cancer, but most of the time the outcome depends on the locoregional recurrence and massive disease in the central compartment. The parathyroid cancer is quite rare, less than 1%, in patients undergoing parathyroidectomy. The diagnosis of parathyroid cancer is made by pathological features but the most certain method of diagnosis of a malignant tumor of the parathyroid is the identification of secondary deposits. The incidence of distant metastasis is difficult to determine due to the rarity of this condition, but the most common site is the lung. Patients with distant metastasis have recurrent progressive hypercalcemia along with high parathormone level.
Noncervical Lymph Node Metastasis from Head and Neck Cancer
Authors: Kowalski Luiz P.
Published: April 2003

Nonregional lymph node dissemination must be classified as distant metastasis but axillary and mediastinal metastases can be part of a regional dissemination of the disease. Metastases to lymph nodes of the upper mediastinum are very common among patients with subglottic, hypopharynx and thyroid carcinomas. Axillary metastases are found at autopsy in 2–9% of the patients who died of head and neck squamous cell carcinoma (SCC) and are frequently associated with skin implantation in aggressive recurrent head and neck carcinomas. The possible explanations for this location of metastasis were retrograde dissemination due to lymph system blockage, further tumor dissemination after a parastomal recurrence, hematogenous dissemination, and metastasis from a second primary tumor. Patients with distant metastasis have been considered incurable and only palliative treatment was instituted. Treatment planning for cases with axillary metastasis must take in consideration the likelihood of other regional recurrences and/or distant metastasis. Also, the presence of a second primary tumor must be ruled out. Whenever axilla is the only site of cancer recurrence, a standard axillary dissection must be considered. Upper mediastinal metastases from subglottic and hypopharyngeal cancer are managed by paratracheal and mediastinal dissection through the neck and postoperative radiotherapy.
Voice Outcome following Lateral Laryngotomy to Remove Teflon Granuloma
Authors: Billante Cheryl R. , Burkard Kimberly A. , Clary Janye M. , Childs Prudence , Netterville James L.
Published: April 2003

Formation of a Teflon granuloma may lead to progressive dysphonia and airway compromise. Excision of the granuloma by lateral laryngotomy allows preservation of the uninvolved lamina propria. A sternothyroid muscle flap or Silastic implant to medialize the vocal fold restores a straight glottal edge and optimizes voice production. Fifteen patients underwent removal of a Teflon granuloma via a lateral approach. Analysis of data revealed improved acoustic and aerodynamic parameters of voice following surgery. Indices of acoustic perturbation were reduced, and vocal pitch normalized. While the dynamic pitch range was unchanged, the capacity to vary loudness was enhanced. Flow rates in speech, abnormally elevated before surgery, normalized after the procedure, and phonation times were significantly longer. Perceptual and stroboscopic data confirmed that voices were improved, but not normal.
[Fluorine-18]Fluorodeoxyglucose Positron Emission Tomography, DNA Ploidy and Growth Fraction in Squamous-Cell Carcinomas of the Head and Neck
Authors: Jacob Roland , Welkoborsky Hans J. , Mann Wolf J. , Jauch Martina , Amedee Ron
Published: April 2003

Background: Positron emission tomography (PET) offers an opportunity to examine noninvasively cellular functions with different tracers. [18F]Fluorodeoxyglucose (FDG) is most commonly used in identifying malignant tumors. Several tumor biologic characteristics (tumor cell viability, growth faction, treatment response to radiation, cell membrane dysfunction, recurrence rate) are suggested to be characterized by [18F]FDG PET. The aim of this study was to assess which other tumor biologic characteristics of squamous-cell carcinoma of the head and neck are correlated with [18F]FDG PET. Methods: [18F]FDG PET was performed in 14 patients with squamous-cell carcinomas of the upper digestive tract (TNM classification T2–T4, N1–N3). After attenuation correction, predefined areas of the tumor were semiquantitatively analyzed by the technique of the region of interest and calculated as standard uptake values (SUV). Afterwards, 5 biopsies of different tumor regions were obtained during endoscopy in each patient under general anesthesia, and a correlation between SUV of [18F]FDG PET and tumor biologic parameters was attempted. These parameters included: quantitative DNA measurements (i.e. 2c deviation index, 5c exceeding rate), immunohistochemical assessment of growth fraction (i.e. Ki67-MIB-1, PCNA) along with morphological tumor front grading. Results: The results revealed a marked variation of proliferation and cellular differentiation in various regions of the tumor for all parameters examined. There was a close correlation between [18F]FDG uptake and growth fraction (r = 0.83 for Ki67-MIB-1 and r = 0.8 for PCNA). A poor correlation was found between DNA aneuploidy (r = 0.4) or tumor front grading (r = 0.12) and [18F]FDG uptake. Conclusions: Our results confirm previous clinical and histologic observations that squamous-cell carcinomas of the upper digestive tract are heterogeneous tumors. Ki67 antigen, which has been shown to be of predictive value for proliferation and individual prognosis, correlated with [18F]FDG uptake. Using [18F]FDG PET, the main proliferation centers of inhomogeneous squamous-cell carcinomas could be identified with possible clinical implications for patient management.
Clinical Outcome of Laryngotracheal Separation for Intractable Aspiration Pneumonia
Authors: Yamana Takayo , Kitano Hiroya , Hanamitsu Masakazu , Kitajima Kazutomo
Published: April 2003

Objectives: To confirm that laryngotracheal separation (LTS) is a satisfactory treatment for patients with intractable aspiration pneumonia, even though it does not require tracheoesophageal anastomosis. Study Design: Retrospective. Methods: Nine patients with intractable aspiration pneumonia underwent LTS at our institution from 1996 to 1999. Two patients underwent postoperative barium swallow radiography. Results: Neither halitosis nor stimulation of the cough reflex occurred due to pooled secretions in the blind pouch of the proximal tracheal segment. Barium swallow radiography confirmed that the secretions drained within 40 min by swallowing or a change in patient position. Conclusion: LTS is a satisfactory solution to the problem of chronic aspiration. Neither pooled secretions in the proximal tracheal segment nor fistula formation were significant postoperative problems.
Hearing Loss in Relation to Round Window Membrane Morphology in Experimental Chronic Otitis media
Authors: Nordang Leif , Anniko Matti
Published: April 2003

The present study was performed to test the effect of single and repeated Pseudomonas aeruginosa exotoxin A (PaExoA) instillations in the middle ear of the rat. The hearing level was examined by the ABR technique, round window membrane (RWM) thickness was measured and morphology was studied by light microscopy. The results showed both reversible and permanent hearing loss (HL). In animals that received a single dose of PaExoA, the RWM thickness doubled initially and remained thickened during the observation period. When PaExoA was instilled on several occasions, RWM thickness doubled, before decreasing to near-control levels. This study confirms the toxicity of PaExoA and the partially reversible HL occurring after a single application of the toxin. The diminished effect of repeated toxin instillations – despite the decreasing thickness of the RWM – is discussed.
Quantitative Molecular Analysis of Laser-Microdissected Paraffin- Embedded Human Tissues
Authors: Lehmann Ulrich , Bock Oliver , Glöckner Sabine , Kreipe Hans
Published: April 2003

Laser microdissection enables the contamination-free isolation of morphologically defined pure cell populations from archival formalin-fixed paraffin-embedded tissue specimens. Cells isolated by this method have been characterized by a wide variety of qualitative molecular assays, e.g. loss of heterozygosity, point mutations, clonality and lineage origin. The recently introduced real-time PCR technology renders the reliable quantification of very small amounts of nucleic acids possible. Several groups including our own showed that this technique can be successfully applied for the quantification of DNA and RNA isolated from microdissected archival tissue sections, even after immunohistochemical staining. The exact analysis of quantitative changes of nucleic acids during the course of pathological alterations has thus become possible. In many situations these quantitative changes can be expected to be more important than qualitative changes. The new technology for the quantification of structural genomic alterations and changes in the gene expression pattern in conjunction with microdissection have equipped morphologists with a powerful tool to study reactive and neoplastic changes of tissues.
Laser Microdissection as a New Approach to Prefertilization Genetic Diagnosis
Authors: Clement-Sengewald Annette , Buchholz Tina , Schütze Karin
Published: April 2003

The genetic status of oocytes can be determined by polar body (PB) analysis. Following PB extraction, a genetic evaluation is performed. As each PB contains the complementary genetic material of the oocyte, PB analysis reveals information about its genetic status. Genetically altered oocytes may then be excluded from in vitro fertilization. The aim of our study was to evaluate laser microdissection as a tool for PB extraction purposes. Compared to the PB extraction with a sharp-ending pipette only, we could show that laser microdissection of the zona pellucida (laser zona drilling) with a UV-A laser and subsequent extraction with a blunt-ending pipette decreases the degeneration rate of oocytes. It is shown that laser pressure catapulting of extracted PB enables their contact-free transfer into tubes, thus decreasing the risk of contamination for further analysis.
Primary Thymic Endocrine Failure in HIV-1-Infected Children
Authors: Consolini Rita , Legitimo Annalisa , Milani Monica
Published: April 2003

Thymulin, an essential hormone for the T lymphocyte differentiation process and function, was evaluated to asses thymic endocrine function in a cohort of 17 HIV-1-infected children aged between 2 months and 14 years, 18 seroreverted subjects and 47 normal controls. The rosette inhibition assay by Dardenne and Bach (1975) is the only method available to evaluate the biologically active form of this hormone (thymulin or Zn-facteur thymique sérique, Zn-FTS), as immunoassays cannot discriminate between thymulin and the inactive form of the hormone not containing Zn (FTS). HIV-1 patients presented undetectable or significantly lowered plasma levels of thymulin. Plasma zinc levels were significantly reduced in patients although inactive, zinc-unbound thymulin molecules were not demonstrated. The investigation of inhibitory anti-thymulin molecules performed in all patients was negative. Thymulin titers did not correlate with CD4+ lymphocyte count at the different disease stages. This study suggests that a primary thymic endocrine deficiency is present in HIV children. The critical importance of these results in assessing disease progression and a potential therapeutic approach are discussed.