bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose Scheduling – Herceptin®
Authors: Leyland-Jones Brian
Published: April 2003

Preclinical and phase I/II studies of Herceptin® demonstrated a dose-related, non-linear pharmacokinetic profile. The results of a dose-finding study supported a regimen comprising an initial intravenous (i.v.) dose of 4 mg/kg with subsequent weekly doses of 2 mg/kg. However, pharmacokinetic and safety data suggested that increased dose and reduced frequency of Herceptin administration are feasible. In addition, evidence shows that Herceptin plus paclitaxel has additive antitumor efficacy in vitro, and this regimen produces significant clinical benefits. These observations form the rationale for conducting a phase I/II trial of Herceptin (8 mg/kg initial dose, 6 mg/kg maintenance dose) plus paclitaxel, both given 3-weekly. Preliminary results are promising, with serum trough Herceptin concentrations being similar and AUC being greater than those observed with weekly Herceptin plus 3-weekly paclitaxel. Two further trials are proposed: 3-weekly Herceptin as first-line monotherapy of metastatic breast cancer; and 3-weekly Herceptin with the oral 5-fluorouracil derivative, Xeloda® (capecitabine). Subcutaneous (s.c.) administration of Herceptin would further simplify administration and studies are also underway to clinically evaluate s.c. administration of Herceptin in combination with paclitaxel. With the recent development of oral taxanes, it is predicted that combinations including an oral taxane, Xeloda and either 3-weekly or possibly s.c. Herceptin may become future therapies for breast cancer patients.
First-Line Herceptin® Monotherapy in Metastatic Breast Cancer
Authors: Vogel Charles L. , Cobleigh Melody A. , Tripathy Debu , Gutheil John C. , Harris Lyndsay N. , Fehrenbacher Louis , Slamon Dennis J. , Murphy Maureen , Novotny William F. , Burchmore Michael , Shak Steven , Stewart Stanford J.
Published: April 2003

The pivotal phase II and III Herceptin® trials proved the efficacy and safety of second- or third-line single-agent Herceptin and first-line Herceptin in combination with chemotherapy, respectively. In the current trial, 114 patients were randomized to one of two dose groups of first-line Herceptin monotherapy: standard dose of 4 mg/ kg initial dose followed by 2 mg/kg intravenous (i.v.) weekly; or high dose of 8 mg/kg initial dose followed by 4 mg/kg i.v. weekly. The regimen was generally well tolerated. A similar incidence of adverse events was demonstrated in the two dose groups with the possible exception of acute infusion-related events such as fever and chills as well as rash and dyspnea, which appear to be more prevalent in the higher dose group. The overall response rate was 26% and response rates were similar between the two dose groups (24% for the standard Herceptin dose group and 28% for the high Herceptin dose group). Subgroup analysis determined a higher response rate in IHC 3+ patients (35%) and FISH-positive patients (41%). When women with stable disease for ≧6 months were included with responders, the clinical benefit rate in IHC 3+ patients was 47%. Median survival was 24.4 months, which is comparable with the survival rate seen in the pivotal phase III combination trial (25 months). Therefore, single-agent Herceptin is an important new option for the first-line treatment of HER2-positive metastatic breast cancer patients.
The Predictive Value of HER2 in Breast Cancer
Authors: Piccart Martine , Lohrisch Caroline , Di Leo Angelo , Larsimont Denis
Published: April 2003

Measurement of molecular markers predictive of response to therapy should enable more selective and effective utilization of anticancer agents. The predictive value of HER2 remains a complex and inconclusive subject. In metastatic breast cancer, HER2-positive, ER-positive patients can show responses to endocrine treatment, but experience shorter time to progression and survival than HER2-negative patients. In the adjuvant setting, weak, retrospective evidence suggests that tamoxifen is potentially harmful in HER2-positive patients and that there is no benefit from prolonged tamoxifen therapy. It has not yet been demonstrated conclusively that HER2 positivity increases resistance to adjuvant cyclophosphamide, methotrexate, 5-FU (CMF), but there are indications that HER2-positive patients benefit more from adequately dosed anthracyclines than from CMF. The greatest value of HER2 as a predictive marker lies in the prediction of response to therapies that target HER2, such as Herceptin®. Patients with strongly HER2-positive breast cancer derive significant clinical benefit from single-agent and combined Herceptin therapy. HER2 testing has become an integral part of the optimal management of the breast cancer patient. Best current practice in adjuvant breast cancer therapy based on the current knowledge of the potential predictive power of HER2 constitutes not denying tamoxifen to HER2-positive, ER-positive patients or CMF to HER2-positive patients. Outside of clinical trials, adequately dosed anthracycline-based chemotherapy is the current preferred adjuvant treatment option for HER2-positive patients.
Role of Herceptin® in Primary Breast Cancer: Views from North America and Europe
Authors: Leyland-Jones Brian , Smith Ian
Published: April 2003

Current therapeutic strategies for primary breast cancer aim to provide improvements in outcome with minimal toxicity to the patient. However, annual relapse rates of up to 12 to 13% during the first 10 years after treatment are seen, and although toxicity has been reduced, it remains a problem in a patient population that is largely asymptomatic. Thus, there is a clear need for more effective therapies. Amplification/overexpression of the human epidermal growth factor receptor-2 (HER2) is an early event in the development of a significant proportion of breast tumors. This abnormality has been shown to have a detrimental effect on prognosis, may predict the outcome of therapies such as tamoxifen and anthracyclines, and provides a target for the novel therapy, Herceptin®. Herceptin is effective and well tolerated in the metastatic setting, making it an ideal candidate for use in adjuvant breast cancer therapy. This has led to the design of a number of trials that aim to provide conclusive evidence as rapidly as possible that Herceptin is well tolerated and effective in the adjuvant setting while also addressing the question of which regimen provides greatest benefit. This review describes these trials and explains how differences in practice between North America and Europe have influenced trial design.
High-Frequency Ultrasound Biomicroscopy versus Ultrasound and Optical Pachymetry for the Measurement of Corneal Thickness
Authors: Pierro Luisa , Conforto Eugenio , Giordano Resti Antonio , Lattanzio Rosangela
Published: April 2003

The aim of this study was to correlate central corneal thickness measurements obtained using optical as well as ultrasound pachymeters and high-frequency ultrasound biomicroscopy (UBM), assuming UBM as reference. Each measurement was performed on 32 patients (60 eyes) by three observers unaware of the other''s results, on 3 different days. Pearson correlation was used. A strong correlation was found between UBM and ultrasound pachymetry measurements (r=0.858), a weaker one between UBM and optical pachymetry (r=0.506). Optical versus ultrasound measurements were poorly correlated (r=0.540). Each correlation was statistically significant (p<0.001). UBM can be used as an accurate and reproducible method for determining corneal thickness.
The Use of Ultrasound Biomicroscopy In Pre-Operative Evaluation of Orbital-Blepharal Neoformations: Report of a Case
Authors: Sabetti Lelio , Toscano Andrea , Specchia Giuseppe , Balestrazzi Emilio
Published: April 2003

In our study we have taken into consideration the use of ultrasound biomicroscopy (UBM) in a case of orbital-blepharal lymphoma. The advantages of this methodology, which is considered a refinement of B scan ultrasonography, compared with other instruments at present available on the market, have been described. We have tried to show how the instrument for biomicroscopic ultrasonography makes it possible to obtain images of the anterior segment of the eye in every detail; it is, therefore, capable of giving us information once only available by means of examining histopathological sections. Apart from the advantages, in this work we have also described the limits of this methodology, which in order to allow an accurate diagnosis must always be accompanied by the traditional ocular echography.
Ultrasound-Biomicroscopic Evaluation of Filtering Blebs after Laser Suture Lysis Trabeculectomy
Authors: Avitabile T. , Russo V. , Uva M.G. , Marino A. , Castiglione F. , Reibaldi A.
Published: April 2003

Sometimes in glaucomatous patients treated with trabeculectomy there is no correlation between bleb shape and intra-ocular pressure (IOP). In this study we evaluated the ultrasound biomicroscopy (UBM) features of filtering blebs after laser suture lysis (LSL) trabeculectomy in order to analyse whether its ultrasound-biomicroscopic image can predict the function (IOP). Methods: The Humphrey ultrasound biomicroscope, using a high-frequency (50-Mhz) probe, provides high-resolution images of filtering blebs. A total of 103 filtering blebs after LSL trabeculectomy were analysed by UBM. Taking into account the characteristics of internal reflectivity and scleral flap, we classified the blebs into three groups (good, fair, poor) that indicate the bleb function and correlated this UBM pattern with the IOP control (good, borderline, failure). Results: There was a statistically significant corelation between the UBM classification of function and the IOP control level. Both well-functioning and failed trabeculectomies could be identified by UBM. The UBM images of eyes with good IOP control are characterized by better visibility of the route under the scleral flap and a low reflectivity inside the bleb. Conclusions: In accordance with previous studies, we believe that UBM can be a useful method to study and explain the mechanisms of filtering structures and, together with IOP control, to evaluate the bleb function.
Extraocular Muscle Size Comparison between Normal and Myopic Eyes Using Standardized A Scan Echography
Authors: Pierro Luisa , Zaganelli Elisabetta , Tavola Alessandra , Muraglia Mario
Published: April 2003

The aim of this study was to establish the range of diameters of extraocular muscles in myopic patients and to obtain the baseline data to follow progression or regression of pathologies involving them. Standardized A scan and B scan ultrasound was used to measure the thickness of straight extraocular muscles at the muscle belly. No statistical differences were seen between right and left eyes. We found no consistent correlation with age or with axial length in the control or in the myopic patients (p>0.05). Diameters in myopic and control eyes were similar. This lack of difference between myopic and control muscle sizes means that we can obtain accurate measurements also from myopic patients.
Echobiometric Evaluation of the Axial Length of the Eye and Intraocular Lens Calculation in Pseudophakic Eyes: Our Experience
Authors: Polizzi A. , Schenone M. , Ciurlo C. , Bertagno R. , Molfino F. , Camoriano G.P. , Saccà S.C.
Published: April 2003

Intraocular lens (IOL) power calculation in 46 pseudophakic eyes (extracapsular cataract extraction with IOL in posterior chamber), utilizing a Javal keratometer, a Sonomed A 2000 echobiometer (probe 10 MHz, velocity=1,548 m/s) and the SRK2 formula, although there was a statistically significant reduction of the axial length, both in normal and hyperopic eyes, demonstrated no statistically significant differences of IOL power, when compared to the power previously calculated in the phakic eye.
Recurrent Eyelid Basal Cell Carcinoma with Sclerochoroidal Infiltration: Echographic Findings
Authors: Mantovani E. , Doro D. , Milizia E. , Steindler P.
Published: April 2003

In an 82-year-old woman with a recurrent right lid basal cell carcinoma infiltrating the upper temporal orbit, a solid yellowish lesion was found ophthalmoscopically in the superotemporal periphery of the right eye. On standardized echography examination, the 2.5-mm elevated subretinal lesion was medium to high reflective with irregular structure, whereas the adjacent orbital mass was medium to low reflective and the sclera was thinned with at least one passage between the orbital and ocular lesions. To our knowledge, this is the first echographic report of sclerochoroidal infiltration from a lid basal cell carcinoma.
Ultrasonographic Features and Patterns of Regression after Conservative Treatment of Retinoblastoma
Authors: Motolese Eduardo , Addabbo Giuseppe , Manes Carlo
Published: April 2003

The authors analyze the echographic features relative to some cases of retinoblastoma treated with conservative therapy in order to monitor the regression of the tumor consequent to the treatment.
Sensitivity and Specificity of Ultrasonography, Fluorescein Videoangiography, Indocyanine Green Videoangiography, Magnetic Resonance and Radioimmunoscintigraphy in the Diagnosis of Primary Choroidal Malignant Melanoma
Authors: Romani A. , Baldeschi L. , Genovesi-Ebert F. , Rizzo S. , Nardi M.
Published: April 2003

The prognosis of primary choroidal malignant melanoma (PCMM) is fatal if no early reliable diagnosis is performed. Any incisional biopsy is impossible, and diagnosis is only based on instrumental examinations. The purpose of this study is to evaluate the reliability of ultrasonography, fluorescein videoangiography (FV), indocyanine green videoangiography (ICGV), magnetic resonance (MR) and radioimmunoscintigraphy (RIS) in the diagnosis of PCMM in a series of 12 eyes in which the tumor was suspected. A presumed diagnosis of PCMM was made when a positive result was obtained with 3 or more methods. The presumed diagnosis was then compared with histological findings (true value) in 4 enucleated eyes. The sensitivity and specificity of every single method were evaluated comparing its results with the final presumed diagnosis and with the histological findings. Sensitivity and specificity of every single method have been expressed as percentage of correspondence with the presumed diagnosis. Sensitivity was 100% for ultrasonography, MR, FV, ICGV and 67% for RIS. Specificity was 92% for ultrasonography, 87% for RIS, 83% for MR and 82% for FV and ICGV. This study indicates that the ophthalmologist can obtain a good diagnostic reliability in the case of PCMM using only ultrasonography, FV and ICGV. Besides MR and RIS are important adjunctive methods to ophthalmological investigations for the diagnosis of PCMM.
Lens and Retinal Changes in the WBN/Kob Rat (Spontaneously Diabetic Strain)
Authors: Miyamura Noritake , Amemiya Tsugio
Published: April 2003

Male WBN/Kob rats represent a spontaneously diabetic strain with hyperglycemia, cataracts, nephropathy, neurophathy, pancreatic fibrosis and hyperlipemia. Cataracts and retinal changes in WBN/Kob rats were examined by light and electron microscopy to evaluate the ocular complications. Lens opacity was present in the posterior subcapsular and center of the anterior cortex of male 14-month-old WBN/Kob rats. Light and transmission electron microscopy showed swelling and irregularity of lens fibers. Scanning electron microscopy revealed that lens fibers were irregular and had many granules and bulging processes of various sizes on the cortical side of the opacified region. The nuclear side of the opacified region showed spongy changes and complete absence of lens fibers. Electron microscopy showed retinal degeneration in the photoreceptor outer segments of 1-month-old male WBN/Kob rats. Light microscopy showed thin outer segments and outer nuclear layers in 5-month-old rats, and electron microscopy revealed severe degeneration in the outer segments. The retinas of 11-month-old rats were thinner; the outer plexiform layer was very thin; the photoreceptor cell nuclei in the outer nuclear layer had decreased to one layer and were almost in contact with the inner nuclear layer nuclei, while the visual cells had disappeared. Retinal degeneration had progressed even further in 14-month-old rats, and very few photoreceptor cell nuclei remained. The retinal capillary lumens were small, and their pericytes had thickened basement membranes. The basement membranes of retinal capillaries from WBN/Kob rats were significantly thicker than those from control Wistar rats (p < 0.0001). Although this rat has spontaneous diabetic features, such as cataracts, its retinal changes look more degenerative.
Effectiveness of Eye Drops Protective against Ultraviolet Radiation
Authors: Daxer Albert , Blumthaler Mario , Schreder Josef , Ettl Armin
Published: April 2003

Background: To test the effectiveness of commercially available ultraviolet (UV)-protective eye drops (8-hydroxy-1-methylchinolinium methylsulphate) which are recommended for protection against both solar and artificial UV radiation. Methods: The spectral transmission in the wavelength range from 250 to 500 nm was investigated in 1-nm steps using a high-resolution double monochromator with holographic gratings of 2,400 lines/mm and a 1,000-watt halogen lamp as light source. The transmission spectrum was measured for different values of the layer thickness. Results: The transmission of a liquid layer of about 10 µm, which corresponds to the thickness of the human tear film, shows a cut-off at 290 nm with a transmission of about 25–50% at shorter wavelengths. For wavelengths longer than 290 nm the transmission is higher than 90%. The threshold time ratio for keratitis formation with and without eye drops is above 0.93 considering solar radiation on the earth’s surface and above 0.65 considering radiation from arc-welding, respectively. Discussion: The transmission spectrum of the eye drops under realistic conditions does not show a protective effect against solar UV radiation. However, there exists reduction of UVC radiation in the spectral range typical of artificial UV sources such as arc-welding. We cannot recommend the application of these eye drops as an UV-protective aid against eye damage by solar UV radiation.
Systemic Murine Cytomegalovirus Infection of Mice with Retrovirus- Induced Immunodeficiency Results in Ocular Infection but Not Retinitis
Authors: Dix Richard D.
Published: April 2003

Experiments were performed to explore the ability of murine cytomegalovirus (MCMV) to disseminate to the eye following intravenous inoculation and to cause infection of ocular tissues and necrotizing retinitis in C57BL/6 mice with retrovirus-induced immunodeficiency syndrome (MAIDS). Although infectious virus could be detected in whole eye homogenates of mice with MAIDS at 10 days after intravenous MCMV inoculation, a recombinant MCMV (RM461) that carries an MCMV IE1 promoter-LacZ insert was used as a tracer virus to confirm direct infection of ocular tissues. Evidence for MCMV replication (determined by RM461-induced expression of β-galactosidase) was consistently observed in the nonpigmented epithelium of the ciliary body of the eyes of MAIDS animals at 14 days after infection. In sharp contrast, however, the neurosensory retina was spared and necrotizing retinitis failed to develop. These findings demonstrate that systemic MCMV infection of mice with MAIDS results in ocular MCMV infection without development of ocular MCMV disease. Conversion of occult subclinical MCMV infection of ocular tissues to overt clinical MCMV retinitis may require as yet unidentified cofactor(s). Identification of these cofactors could lead to more innovative therapeutic approaches for prevention and/or treatment of CMV retinitis in patients with AIDS.
Is Whitnall’s Ligament Responsible for the Curved Course of the Levator palpebrae superioris Muscle?
Authors: Ettl A. , Zonneveld F. , Daxer A. , Koornneef L.
Published: April 2003

Background and Purpose: The levator palpebrae superioris (LPS) muscle courses anteriosuperiorly to culminate cranial to the posteriosuperior surface of the globe from where it courses anterioinferiorly to the tarsal plate. Whitnall’s superior transverse ligament (STL) has been suggested to suspend the LPS at its culmination. If this was the case, one would expect the STL to be located near the culmination of the LPS. In order to elucidate this functional aspect of the STL, the spatial relation of the STL to the LPS muscle is investigated in this study. Methods: Surface coil MRI in an oblique sagittal plane along the optic nerve was performed in 6 orbits from 3 human cadavers in which the STL was marked with synthetic material. Results: The MR images showed that in human cadaver specimens the STL is situated in the anterior descending portion of the LPS. Conclusion: This result suggests that the STL does not suspend the LPS at its culmination and is therefore not responsible for the curved course of the muscle.
Effect of Retinoic Acid on Proliferation and Polyamine Metabolism in Cultured Bovine Retinal Pigment Epithelial Cells
Authors: Yasunari Takaharu , Yanagihara Nobuyo , Komatsu Toshiro , Moriwaki Mitsuyasu , Shiraki Kunihiko , Miki Tokuhiko , Yano Yoshihisa , Otani Shuzo
Published: April 2003

Reports regarding the effect of all-trans-retinoic acid (RA) on the cell growth of retinal pigment epithelial cells (RPE) have been contradictory. The aims of this study are to clarify the in vitro effect of RA on RPE cells and to examine polyamine metabolism after RA stimulation. A 4-day incubation of fetal-calf-serum (FCS)-stimulated RPE cells with 10 or 25 µM RA significantly increased both cell number and [3H]thymidine incorporation. RPE cells grown over an extended period for 8 days also increased in number and reached full confluency. However, if the incubation was further extended to 12 days, no further increase in cell number was detected. RA treatment of FCS-stimulated RPE cells shifted the peak of ornithine decarboxylase (ODC) activity from 16 to 4 h. S-adenosylmethionine decarboxylase (SAMDC) activity and spermidine/spermine N1-acetyltransferase (SAT) activity of RA-treated RPE cells were significantly greater until 8 and 16 h after incubation, respectively. The putrescine content was significantly increased in RA-treated RPE cells up until 24 h, while spermidine, spermine and N1-acetylspermidine contents were significantly increased until 16 h. Our findings suggest that RA treatment increases the intracellular polyamine concentration of RPE cells via activation of ODC, SAMDC and SAT and that this results in the promotion of RPE cell growth until the cells reach full confluency.
Pharmacokinetics of Azithromycinin Rabbit Lacrimal Glands and Conjunctiv a
Authors: Karcioglu ZeynelA. , Ahmed WaelS. , Raines Dale , El-Yazigi Adnan
Published: April 2003

Purpose and Background: To measure azithromycin levels in rabbit lacrimal and Harder glands, conjunctiva and plasma after a single oral dose of 20 mg/kg. Drug levels in lacrimal gland tissue are significant in trachoma because the gland may be involved in the disease process and it is the source of tears by which the drug is carried to the external eye. Methods: Lacrimal and Harder glands, conjunctiva and plasma were collected from New Zealand white female rabbits at 24, 48, 72, 96 and 144 h following a single oral dose of azithromycin (20 mg/kg). Azithromycin levels in tissue and plasma were measured using high-performance liquid chromatography (HPLC) electrochemical detection. Results: Azithromycin levels peaked within the first 24 h in all tissues and plasma assayed. The highest concentration was in the lacrimal gland (6.2 µg/g, SD ± 0.8), followed by Harder gland (4.4 µg/g, SD ± 0.8), conjunctiva (0.9 µg/g, SD ± 0.5) and plasma (0.06 µg/g, SD ± 0.03). These concentrations reached their lowest measured levels at 120 and 144 h. Conclusion: Azithromycin levels measured throughout the 144 h after dosing were consistently above the minimum inhibitory range (MIC) for Chlamydia trachomatis (0.03–0.25 µg/ml) in the lacrimal glands, while the conjunctiva maintained a concentration above the MIC for 96 h and stayed within MIC levels for 144 h.
Image Analysis of Implanted Rigid and Foldable Intraocular Lenses in Human Eyes Using Scheimpflug Photography
Authors: Klos K.M. , Richter R. , Schnaudigel O.-E. , Ohrloff C.
Published: April 2003

We evaluated the quality of imaging posterior chamber intraocular lenses (PC IOL) by Scheimpflug photography. We took photographs of 190 rigid or foldable PC IOLs using the Scheimpflug system EAS-1000 from Nidek and provided digital image analysis. We found a good imaging of PC IOLs and the cristalline lens capsule, data obtained by digital image analysis were reliable and reproducible and Scheimpflug photography could be demonstrated as a sensitive tool to show any irregularities of IOL material. Thus, we found in foldable IOLs ‘glistenings’, which did not have any influence on functional results and we could distinguish them from lens damage. We propose to use Scheimpflug tests regularly for the examination of implanted new types of IOLs.
Localised Fibre Cell Swelling Characteristic of Diabetic Cataract Can Be Induced in Normal Rat Lens Using the Chloride Channel Blocker 5-Nitro-2-(3-Phenylpropylamino) Benzoic Acid
Authors: Tunstall Mark J. , Eckert Reiner , Donaldson Paul , Kistler Joerg
Published: April 2003

Chloride channels are known to be involved in the regulated volume decrease that occurs when the rat lens is exposed to hypotonic challenge. We now report that chloride channel blockage makes the rat lens gain water under isotonic conditions, suggesting that chloride and water fluxes may also play an important role under resting conditions. Histological comparison of hypotonically and isotonically swollen rat lenses revealed a significant difference: in the former, fibre cells were swollen from the periphery inwards, while in the latter, swollen fibre cells were confined to a discrete cortical zone which was located 150–200 µm from the lens surface with cells on either side of this zone appearing unaffected. This localised fibre cell swelling is remarkable because of its similarity to the situation in the diabetic rat lens.
Alpha-Tocopherol Derivatives in an Experimental Model of Filtering Surgery
Authors: Pinilla I. , Larrosa J.M. , Polo V. , Honrubia F.M.
Published: April 2003

Purpose: To evaluate the efficiency and reliability of α-tocopherol in an experimental model of glaucoma filtering surgery. Methods: Thirty pigmented rabbits were randomly divided into three study groups. Twenty-four hours before surgery, the animals were injected subconjunctivally with 0.5 ml of solution that depended on the group of treatment: group I (n = 10), 0.75% ethanol in balanced saline solution (BSS); group II (n = 10), 100 mg α-tocopherol acetate (ATA) in 0.75% ethanol in BSS; group III (n = 10), 100 mg α-tocopherol acid succinate (ATS) in 0.75% ethanol in BSS. The animals were followed during 30 days (intraocular pressure, IOP; filtering surgery; inflammatory reaction). Results: IOPs were significantly lower in the treatment groups (ATA and ATS) than in the control group from days 7 and 10, respectively, till the end of the study. On day 7, the mean IOP in the ATA group was 15.8 versus 22.1 mm Hg in the control group. On day 10, the mean IOP in the ATS group was 15 versus 22.78 mm Hg in the control group. Filtering blebs showed statistically significant differences between the control and treated groups from day 5 to day 16. Conclusions: α-Tocopherol (ATA and ATS) showed better IOP control and bleb survival in this experimental model of filtering surgery.
Ophthalmological Effects of High Altitude
Authors: Karaküçük Sarper , Mirza G. Ertuğrul
Published: April 2003

High altitude has various effects on human beings. Altitude-related illnesses are a frequent cause of morbidity and occasional mortality in travelers to high altitudes throughout the world. The mountaineers all around the world are familiar with this condition, which is called acute mountain sickness (AMS). The primary altitude illnesses are AMS, high-altitude pulmonary edema and high-altitude cerebral edema. Altitude has potential undesired ophthalmological effects. The pathogenesis of these syndromes remains unclear despite considerable research in this field. Most of these problems are primarily preventable with an adequate level of information before and during travel. Further studies are needed to reveal the exact relationship between high altitude and ophthalmological findings. In this article, ophthalmological effects of high altitude, likely to be encountered by mountaineers as well as other enthusiasts of high altitude sports are reviewed. Emphasis on aviation and aerospace medicine is briefly given under related subtitles.
Mechanism of Endothelin 1 Production in the Cochlea of Rats
Authors: Jinnouchi Ken
Published: April 2003

The purpose of this study was to elucidate the mechanism of endothelin 1 (ET1) production in the cochlea of rats. Animals were anesthetized with pentobarbital sodium intraperitoneally and sacrificed by cardiac perfusion with warm saline followed by periodate-lysine-paraformaldehyde. The temporal bones and kidneys were fixed overnight in the same fixative, decalcified with 5% EDTA and embedded in paraffin. Immunohistochemical staining was performed using the labeled streptavidin biotin method to detect the localization of big endothelin 1 (BET1), ET1 and endothelin-converting enzyme 1 (ECE1). Immunoreactivity for BET1, ET1 and ECE1 was localized to the small vessels of the bony labyrinth adjacent to the spiral ligament. Immunohistochemistry for ET1 and BET1 was also localized to the spiral ligament. These results suggest that ET1 may be produced in the small vessels of the bony labyrinth adjacent to the spiral ligament and may play an important role in the cochlear function.
Endoscopic CO2 Laser Surgery for Large Internal Laryngocele
Authors: Hirvonen Timo Petteri
Published: April 2003

The laryngocele is a benign air-filled dilatation of the saccule of the laryngeal ventricle. Its appearance may be related to increased intralaryngeal pressure due to chronic straining. The internal laryngocele is confined to the false vocal cord, and it does not pass through the thyrohyoid membrane. The most common symptoms for internal laryngocele are hoarseness and dysphagia. Large internal laryngoceles may also cause airway compromise, especially when complicated with infection. Endoscopic laser surgery is an acceptable mode of treatment even for large internal laryngoceles as in the present case.
Cortical Transcranial Magnetic Stimulation of the Frontalis Muscle: Characteristic Features and Details on Motor-Evoked Potentials of the Forehead
Authors: Rödel R. , Laskawi R. , Markus H. , Wenke Karin
Published: April 2003

The effect of coil position on the head surface along the interaural line on motor-evoked potentials (MEPs) of the frontalis muscle due to cortical transcranial magnetic stimulation was investigated in 16 healthy subjects. Bilateral reproducible responses could be observed in all subjects investigated at coil positions varying from 2 to 12 cm lateral to the vertex. MEP amplitudes of the frontalis muscle offered no significant side differences neither in amplitude nor in onset latency. Despite a considerable overlap, a statistically significant separation (p < 0.0001) of the two areas from which reproducible MEPs of upper and lower mimetic muscles could be elicited was evident for the calculated mediolateral center with the frontalis muscle area being placed more medially. Our findings are in accordance with anatomical studies indicating a predominance of corticonuclear descending fibers to lower but not to upper facial motoneurons.
Expression of the Voltage-Dependent Chloride Channel ClC-3 in Human Nasal Tissue
Authors: Oshima Takeshi , Ikeda Katsuhisa , Furukawa Masayuki , Suzuki Hideaki , Takasaka Tomonori
Published: April 2003

In the present study, ClC-3, one of the voltage-dependent chloride channels, was identified in human nasal tissue. In situ hybridization and immunohistochemical investigations demonstrated the localization of ClC-3 in the serous acini and ductal portions of submucosal nasal glands, which are the primary source of nasal secretion. Our data suggest that this channel contributes to nasal secretion via chloride transport. Its dysfunction might lead to abnormal nasal secretion in such pathological states as sinusitis.
Evaluation of a New Method for Assessing Symptoms
Authors: Hallén H. , Djupesland P. , Kramer J. , Toll K. , Graf P.
Published: April 2003

Background: Many studies in rhinology are based on results from symptom scoring. Numerous methods are used to estimate symptoms. With some of them the patients choose between various alternatives for estimating the severity of their symptoms, but the commonest method is the visual analogue scale (VAS), which is regarded as reliable. Methods: In this study, we evaluate a new method for assessing symptoms, with which the patient uses the telephone to call a computer. We compare the results using the new method with those using symptoms estimation with VAS. Results: The results are based on 487 observations in patients with birch pollen allergic rhinitis in the pollen season. A high correlation was found between the results using the new method and those using the VAS. In a questionnaire, the patients answered questions concerning the two methods. Most patients preferred the new telephone method. They found it easier to estimate their symptoms properly and easier to perform. Conclusion: We conclude that telephone scoring of symptoms is a reliable and adquate method when symptom scoring is used as hard data in a study.
Viral Co-Infection Does Not Reduce the Efficacy of Vaccination against Non-Typeable Haemophilus influenzae Middle Ear Infection in a Rat Model
Authors: Moore Ryka , Lidbury Brett A. , Cripps Allan W. , Kyd Jennelle M.
Published: April 2003

The mucosal vaccination of rodents with killed non-typeable Haemophilus influenzae (NTHi) has been previously shown to enhance live NTHi clearance following middle ear challenge. This study assessed the efficacy of mucosal anti-NTHi vaccination during a concomitant viral infection of the respiratory tract. Animals were mucosally immunised with killed NTHi by intra-Peyer’s patch primary inoculation and lung (intratracheal) boost. At the time of both immunisations rats were also infected intra-nasally with Sendai virus. Concomitant Sendai virus infection did not influence the efficacy of anti-NTHi vaccination mediated clearance of NTHi from the middle ear. This would suggest that immunisation strategies to prevent bacterial middle ear infection would be effective despite the presence of concomitant viral agents.
Endonasal Endoscopic Dacryocystorhinostomy in a Four-Month-Old Infant
Authors: Mladina Ranko , Stiglmayer Neda , Dawidowsky Krsto , Jukic Tomislav , Jurlina Martin , Trupkovic-Fotivec Bozena
Published: April 2003

The authors present a case of endonasal endoscopic dacryocystorhinostomy in a 4-month-old girl suffering from remarkable epiphora, persistent bulging and recurrent abscesses in the medial canthal region of the left eye. All conservative therapeutic attempts failed. Several external incisions were performed in order to solve the acute phases of the inflamed lacrimal sac. The procedure was performed by means of otologic microsurgical instruments under endoscopic control. No silicone stent was used. Ten months after surgery, the girl is doing very well.
Ancillary Procedures in Microscopic Endonasal Orbital Decompression for Thyroid-Associated Ophthalmopathy
Authors: May A. , Zubcov A. , Fries U. , Reimold I. , Weber A.
Published: April 2003

In 35 patients with thyroid-associated orbitopathy, nonresponsive to conservative treatment, an endonasal microscopic approach with bimural osteotomy was performed for decompression in two ways. While in group A the periorbita was resected, and fat septa were cut, in group B periorbital strips were left, and fat septa were respected. In accordance with other authors, resection of the periorbital and cutting fat septa will improve vision and proptosis, but in up to 30% of the patients de novo diplopia occurs. Our data favor the assumption that a more conservative endonasal microscopic decompression of the orbita leaving periorbital strips and fat septa achieves similar good results for reduction of proptosis and visual gain but creates less often de novo diplopia in primary gaze. Based on our experience, rehabilitation for thyroid-associated arbitopathy comprises as a first step orbital endonasal decompression with cooperation of the ophthalmologist, then if necessary as a second step strabismus surgery, and thirdly eyelid repair for scleral show.
Mechanisms of Photoinduced Cochlear Ischemia in the Guinea Pig
Authors: Saito H. , Ogawa K. , Inoue Y. , Kanzaki J. , Harada T. , Hoya N.
Published: April 2003

An experimental model of cochlear ischemia using the photosensitization reaction of rose bengal (RB) is reported. Ischemia was induced by the systemic administration of RB solution and localized irradiation of the cochlea with a green light of specific wavelength for RB activation. After the RB solution was administered, the cochlear blood flow was temporarily increased and then decreased, and the latency of wave I of the auditory brainstem response increased and the amplitude of wave I decreased after RB injection and finally wave I disappeared completely. A histological study revealed thrombus formation in the vessels of the irradiated cochlea not only in the stria vascularis and the spiral ligament, but also in the modiolus. L-Histidine, a scavenger of singlet oxygen (1O2) and hydroxyl radical (·OH), significantly prolonged cochlear dysfunction, but D-mannitol, a specific scavenger of ·OH did not, suggesting that 1O2 has an important role in this reaction.
Distant Metastases from Nasopharyngeal Cancer
Authors: Chiesa Fausto , De Paoli Fiora
Published: April 2003

Undifferentiated carcinoma is the most frequent nasopharyngeal cancer; it has a typical pathognomonic histological pattern, a close relationship to Epstein-Barr virus (EBV), a peculiar natural history and a good prognosis. It has an early tendency to locally spread to the parapharyngeal space. Nodal involvement is highly frequent (70–90%) and bulky regardless of the size of the primary. Literature reports up to 11% distant metastases at presentation and up to 87% at autoptic studies. Pretreatment work-up should include: personal history, clinical and fiberscopic examination, magnetic resonance imaging (MRI) or computed tomography (CT) scan of the base of the skull and neck, histology of the primary and cytology of neck lumps, bone marrow aspiration and biopsy, and EBV serological profile. Clinical and pathological factors predicting possible distant spread are primary tumor and node extension, and treatment failure. Up to now no reliable predictive biological markers have been identified. After treatment, distant metastases are found in about 30% of patients within 5 years and generally have a bad prognosis. Metastatic nodes above the clavicle, in absence of locoregional failure, aggressively treated with chemoradiotherapy, have a disease-free survival longer than 5 years. The following is the suggested posttreatment work-up for early diagnosis of these salvageable patients: clinical and fiberscopic evaluation every 3 months for 2 years and later on every 6 months; skull base and neck MRI or CT scan, and chest CT scan at 6, 12, 18, 24, 36, 48 and 60 months; EBV serological evaluation.
Distant Metastases from Lip and Oral Cavity Cancer
Authors: Betka Jan
Published: April 2003

Distant metastases related to lip carcinomas occur very exceptionally (0.5–2%) and can be expected in cases of advanced tumors with advanced regional disease. Distant metastases from oral cavity carcinomas variy over a broad interval (8–17%) and depend also on the stage of disease. The knowledge of the presence of distant metastases is vital for the planning of further treatment. From a clinical point of view, patients with lip and oral cavity can be divided into a group where the risk of distant metastases is low, and into a high-risk one. In low-risk group patients (stages I, II and III) the risk of the incidence of distant metastases is 3%, and the diagnostic approach should consist of an X-ray of the lungs and liver tests. Further examinations are necessary if there are symptoms suggesting the presence of distant metastases or previous examinations are abnormal. The high-risk group (stage IV) and all patients with locoregional relapse have a risk of distant metastases of approximately 10% and the best treatment consists of a positron emission tomography (PET) scan. If a PET scanner is not available it is recommended to run a computed tomography scan of the lungs and liver tests. If any clinical investigation is abnormal further tests are necessary.
Distant Metastases from Salivary Glands Cancer
Authors: Bradley Patrick J.
Published: April 2003

Patients who present with malignant salivary glands should at their initial assessment have an X-ray of the chest to exclude the possibility of distant metastases. Patients who have other symptoms, bone pain etc., should be appropriately investigated. The likelihood of patients developing distant metastases is associated with high-grade tumors, most commonly adenoid cystic carcinoma, high-grade mucoepidermoid carcinoma, salivary duct carcinoma and tumors sited in the submandibular gland, posterior tongue and pharyngeal tumors. Patients who have had a high-grade tumor treated and survived without locoregional recurrence have the same risk of developing distant metastases as those patients who have locoregional recurrence. Other histological types of salivary tumors are associated with a lower risk of developing distant metastases but a real risk remains lifelong. It is recommended that all patients who have a malignant salivary gland tumor treated, any histology, should be followed up and clinically assessed at least once every 12 months for life.
Distant Metastases from Ear and Temporal Bone Cancer
Authors: Sasaki Clarence T.
Published: April 2003

Cancers of the temporal bone are rare. Cervical metastases occur in approximately 10% of cases and are much more likely once disease extends beyond the confines of the temporal bone. Nonlymphatic spread of squamous cell carcinoma is usually a late event resulting in metastatic deposits in the lung, bone, liver and brain. This chapter discusses detection of distant metastases and provides a recommended schedule for interval patient evaluation.
Heterogeneity of Phospholipase C in the Cochlea of the Guinea Pig
Authors: Oba Toshihiko , Ogawa Kaoru , Inoue Yasuhiro , Kanzaki Jin
Published: April 2003

In the present study, we investigated the presence of phosphatidylinositol-specific phospholipase C (PLC) isoforms in the cochlea of the guinea pig using Western blot analysis and immunocytochemistry. By Western blotting, PLCβ1 and δ1 were expressed in the cochlear sensory epithelia (CSE) and PLCβ1, γ1 and δ1 were expressed in the cochlear lateral wall. By immunocytochemistry of the CSE, PLCβ1-like immunoreactivity was mainly expressed in the outer hair cells (OHCs), but not in the inner hair cells (IHCs). PLCγ1 and δ1 were expressed neither in the OHCs nor in the IHCs. In the cochlear lateral wall, PLCβ1, δ1 and γ1 were expressed in the stria vascularis and the spiral ligament. In addition, PLCβ1, δ1 and γ1 were also present in type I spiral ganglion cells. Based on these results, we discussed the function of these PLC isoforms in the cochlea.
Treatment of Gustatory Sweating with Botulinum Toxin: Special Aspects
Authors: Laskawi Rainer , Rohrbach Saskia
Published: April 2003

Botulinum toxin treatment is an efficient, well-tolerated technique for patients suffering from gustatory sweating, first described by our group. With the experience gained in recent years we were able to improve on some of our skills in the diagnosis and treatment of gustatory sweating and here we wish to focus on some interesting aspects: (1) the necessity for an exact anamnesis before treatment with botulinum toxin to ensure correct treatment; (2) the advantages of Minor`s test in special situations, for example, when sweating occurs in regions of hairy skin, retroauricular, at the back of the auricle and in areas distant from the site of salivary gland surgery; (3) the reduction of pain during treatment using an anesthetic ointment containing lidocaine and prilocaine as active substances; (4) intracutaneous injections in areas anterior to the fascia-protected skin of the lateral face-covering mimetic muscles, and (5) the occasional necessity for short-time reinjection in small areas of persistent sweating.
Histological Grading, Growth Fraction and DNA-Ploidy as Criteria for the Treatment of Pharyngeal and Supraglottic Squamous Cell Carcinomas: A Preliminary, Prospective Study
Authors: Jacob Roland , Welkoborsky Hans-J. , Bittinger F. , Mann Wolf J. , Amedee Ron
Published: April 2003

Background: Individualized treatment for patients with squamous cell carcinomas is most desirable. Biologic parameters of tumors may provide relevant criteria to achieve this goal. The aim of this study was: (1) to avoid elective neck dissection in patients with squamous cell carcinomas of the pharynx and supraglottis staged N0 by ultrasonography; (2) to administer postoperative radiotherapy only in patients staged ‘highly aggressive’ by biologic tumor parameters, in order to reduce patient morbidity and to improve quality of life. Study Design and Methods: This prospective trial was performed in 35 patients (any T stage, N0 or N1 by ultrasonographic examination). Tumor biopsies were taken for histological examination and for evaluation of some biological tumor markers. These parameters comprised DNA cytometric examinations, histological grading of the tumor front and immunohistochemical staining for proliferation markers (MIB1, PCNA). Based on these parameters, tumors were classified into ‘low aggressive’ (group 1) and highly aggressive (group 2) behavior. In all patients, second primaries were excluded by endoscopy, and the presenting tumor was resected with clear margins. In cases of ultrasonographically enlarged lymph nodes, functional neck dissection was performed. When biologic tumor profile showed low aggressive behavior (group 1), no postoperative radiotherapy was advised. In cases of highly aggressive tumors, radiotherapy was recommended postoperatively independent of all other parameters (group 2a and 2b). Results: The average follow-up was 36 months (range 16–65 months). Fifteen patients were included in group 1, 20 patients in group 2. Three patients with highly aggressive tumors who refused RTx were regarded independently (group 2b). In this pilot study of 35 patients, there was no difference in disease-free survival between group 1 and group 2a. Twenty-five of 35 patients were alive with no evidence of disease 29–65 months after treatment (3 died of disease; 5 died of second primary carcinomas; 2 died independent of disease). Eleven of 15 patients survived disease free in group 1, 13/17 in group 2a. In group 2b, 2 out of 3 patients, who were advised but refused postoperative radiotherapy, had recurrences. Conclusions: The results of this preliminary study point towards usefulness of some tumor biologic parameters in decision making for individualized treatment in patients with squamous cell carcinomas.
Vestibular Evoked Myogenic Potentials in Patients with Idiopathic Bilateral Vestibulopathy
Authors: Matsuzaki Masaki , Murofushi Toshihisa
Published: April 2003

Idiopathic bilateral vestibulopathy (IBV) is an acquired bilateral peripheral vestibular disorder of unknown cause. Three patients diagnosed as IBV by neuro-otological examination were reported. They underwent vestibular evoked myogenic potential (VEMP) testing which reflects the functionality of the sacculo-collic pathway. As a result, 2 of the 3 patients showed bilateral absence of VEMPs and one showed unilateral absence. The VEMPs of the 3 patients revealed that IBV affects not only the superior but also the inferior vestibular nerve systems. As previously reported in the cases of vestibular neuritis, VEMP could be useful for classifying IBV according to the function of the inferior vestibular nerve.