bluuebunny/crossref_metadata_2025 huggingface dataset:
Dermal Penetration of Fentanyl: Inter‐ and Intraindividual Variations
Authors: Larsen Rikke H. , Nielsen Flemming , Sørensen Jens A. , Nielsen Jesper B.
Published: November 2003

Abstract: Fentanyl is a potent synthetic opioid that is increasingly being used in transdermal drug delivery systems. The target organ concentration of a drug administered dermally will depend on the rate of dermal absorption and the systemic elimination. We have studied the intra‐ and interindividual variation in dermal penetration of fentanyl in an in vitro model (static diffusion cells) with human skin, and compared the absorption of fentanyl from an aqueous solution with absorption from a commercial patch. The intraindividual variation in dermal penetration of fentanyl in aqueous solution was limited (18%) and no differences in penetration characteristics were observed between breast and abdominal skin. The interindividual variation in dermal penetration of fentanyl was extensive, with maximal fluxes ranging from 21–105 ng/cm2/hr following application of an infinite dose of fentanyl to the donor chamber. Use of transdermal drug delivery systems (patches) reduced the inter‐individual variation. The permeability coefficients after application of fentanyl in aqueous solution and through patches were identical (0.0011 cm/hr). One person had a higher than average penetration rate following patch application, which may indicate that the human skin and not the patch barrier was the rate‐determining factor for the other individuals included in this study.
Glucocorticoids and glucocorticoid receptors: mediators of fatigue?
Authors: Cleare A. J.
Published: November 2003

Fatigue is a common problem; when chronic and disabling, subjects can be categorized as having chronic fatigue syndrome (CFS). Whilst it is most likely a multifactorial condition of biopsychosocial origin, the nature of the pathophysiological component remains unclear. There has been a wealth of interest in the possible hypothalamo–pituitary–adrenal (HPA) axis dysfunction in CFS, and whether such changes may mediate fatigue. On balance, there appears to be reduced cortisol output in a proportion of patients, together with heightened negative feedback and glucocorticoid receptor function. There is evidence for impaired adrenocorticotropic hormone (ACTH) and cortisol responses to a variety of challenges. However, there is no evidence for a specific or uniform dysfunction of the HPA axis. Evidence that these changes may be related to symptom production comes from randomized controlled trials of glucocorticoid replacement therapy, which have shown improvements in fatigue and disability. Given the many factors that may impinge on the HPA axis in CFS, such as inactivity, sleep disturbance, psychiatric comorbidity, medication and ongoing stress, it seems likely that there is not a single or specific change to the HPA axis in CFS and that the observed HPA axis disturbances are of multifactorial etiology. This is further supported by a comparison of neuroendocrine findings in other conditions in which fatigue is prominent, showing both similarities and differences with the pattern in CFS.
Molecular mechanisms of glucocorticoid receptor sensitivity and relevance to affective disorders
Authors: Juruena Mario F , Cleare Anthony J , Bauer Moisés E , Pariante Carmine M
Published: November 2003

Changes in the hypothalamic–pituitary–adrenocortical (HPA) system are characteristic of depression, and in the majority of these patients these result in HPA axis hyperactivity. This is further supported by the reduced sensitivity to the inhibitory effects of the glucocorticoid, dexamethasone (DEX), on the production of adrenocorticotropic hormone (ACTH) and cortisol, during the DEX suppression test and the DEX-corticotropin-releasing hormone (DEX/CRH) test. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GRs in depressed patients. These studies have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of CRH in various brain regions postulated to be involved in the causality of depression. This article summarizes the literature on GR in depression and on the impact of antidepressants on the GR in clinical and preclinical studies, and supports the concept that impaired GR signaling is a key mechanism in the pathogenesis of depression, in the absence of clear evidence of decreased GR expression. The data also indicate that antidepressants have direct effects on the GR, leading to enhanced GR function and increased GR expression. Hypotheses regarding the mechanism of these receptor changes involve non-steroid compounds that regulate GR function via second messenger pathways, such as cytokines and neurotransmitters. Moreover, we present recent evidence suggesting that membrane steroid transporters such as the multidrug resistance (MDR) p-glycoprotein, which regulate access of glucocorticoids to the brain, could be a fundamental target of antidepressant treatment. Research in this field will lead to new insights into the pathophysiology and treatment of affective disorders.
Automatic design of gene-specific sequence tags for genome-wide functional studies
Authors: Thareau Vincent , Déhais Patrice , Serizet Carine , Hilson Pierre , Rouzé Pierre , Aubourg Sébastien
Published: November 2003

Motivation: The availability of complete genome sequences allows the identification of short DNA segments that are specific to each annotated gene. Such unique gene sequence tags (GSTs) replace advantageously cDNAs in microarray transcript profiling experiments. In particular, probes corresponding to individual members of multigene families can be chosen carefully to avoid cross-hybridization events.

Results: The Specific Primer and Amplicon Design Software (SPADS) was constructed to delineate the more divergent regions in each gene by comparing them with a completely annotated genome sequence and to select optimal primer pairs for the polymerase chain reaction amplification of one divergent region per gene. SPADS is a unique integrated tool to design specific GSTs from any public or private genome sequences and allows the user to fine-tune GST size and specificity. SPADS has been used to obtain probes for whole genome and family-wide transcript profiling, as well as inserts for gene-specific knock-out experiments.

Availability: The GENOPLANTE™ SPADS source code and web interface are available upon request. The online version is accessible via http://genoplante-info.infobiogen.fr/spads and via http://oberon.fvms.ugent.be:8080/SPADS/
Linking the growth inhibition response from the National Cancer Institute's anticancer screen to gene expression levels and other molecular target data
Authors: Wallqvist Anders , Rabow Alfred A. , Shoemaker Robert H. , Sausville Edward A. , Covell David G.
Published: November 2003

Motivation: Data mining tools are proposed to establish mechanistic connections between chemotypes and specific cellular functions. Drawing on a previous study that classified the cellular response patterns of growth inhibition measurements log( GI50) from the National Cancer Institute's (NCI's) anticancer screen, we have examined additional data for mRNA expression, sets of known molecular targets and mutational status against these same tumor cell lines to relate chemosensitivity more precisely to biochemical pathways.

Results: Our analysis finds that gene expression levels do not, in general, correlate with log(GI50) measurements, instead they reflect a generic toxic condition. Within the remaining set of non-generic conditions, examples were found where a correlation suggesting a biochemical basis for cellular cytotoxicity could be supported. These included reconfirmation of previously observed associations between mutant and wild-type status of p53, and chemosensitivity to alkylating agents, while extending these results to reveal associations with γ-induced expressions of MDM2, WAF1 and GADD45, signals that were not apparent in measurements of basal mRNA expression levels for any of these genes. Additional examinations revealed that mRNA expression levels directly correlated with paclitaxel chemosensitivity to mitosis, while also identifying additional chemotypes as P-glycoprotein substrates. Our analysis revealed well-known direct associations between p16 mutant status and chemotypes implicated in cell cycle control, and extended these results to include expression levels for three additional tyrosine kinase proteins (TEK, transgelin and hCdc4). Links were also found that suggested associations between chemosensitivity and the endocrine, paracrine ligand–receptor loops, via expression of the adrenergic receptor, calcium second messenger pathways via expression levels of carbonic anhydrase and cellular communication pathways via fibrillin.
BLAST++: BLASTing queries in batches
Authors: Wang Hao , Ooi Beng Chin , Tan Kian-Lee , Ong Twee-Hee , Zhou Lei
Published: November 2003

Summary: BLAST++ is a tool that is integrated with NCBI BLAST, allowing multiple, say K, queries to be searched against a database concurrently. The results obtained by BLAST++ are identical to that obtained by executing BLAST on each of the K queries, but BLAST++ completes the processing in a much shorter time.

Availability:  http://xena1.ddns.comp.nus.edu.sg/~genesis/blast++

Supplementary information:  http://xena1.ddns.comp.nus.edu.sg/~genesis/blast++
Reliability and Validity of a Simulation-based Acute Care Skills Assessment for Medical Students and Residents
Authors: Boulet John R. , Murray David , Kras Joe , Woodhouse Julie , McAllister John , Ziv Amitai
Published: November 2003

Background

Medical students and residents are expected to be able to manage a variety of critical events after training, but many of these individuals have limited clinical experiences in the diagnosis and treatment of these conditions. Life-sized mannequins that model critical events can be used to evaluate the skills required to manage and treat acute medical conditions. The purpose of this study was to develop and test simulation exercises and associated scoring methods that could be used to evaluate the acute care skills of final-year medical students and first-year residents.

Methods

The authors developed and tested 10 simulated acute care situations that clinical faculty at a major medical school expects graduating physicians to be able to recognize and treat at the conclusion of training. Forty medical students and residents participated in the evaluation of the exercises. Four faculty members scored the students/residents.

Results

The reliability of the simulation scores was moderate and was most strongly influenced by the choice and number of simulated encounters. The validity of the simulation scores was supported through comparisons of students'/residents' performances in relation to their clinical backgrounds and experience.

Conclusion

Acute care skills can be validly and reliably measured using a simulation technology. However, multiple simulated encounters, covering a broad domain, are needed to effectively and accurately estimate student/resident abilities in acute care settings.
Tissue Factor and Platelet Glycoprotein Ib-α Alleles Are Associated with Age at First Coronary Bypass Operation
Authors: Donahue Brian S. , Byrne Daniel W. , Gailani David , George Alfred L.
Published: November 2003

Background

Age is a known risk factor for postoperative complications, but the genetic factors that account for variability in age at presentation for surgery have not been characterized. Because thrombosis is a critical process in the development of coronary syndromes, the authors hypothesized that patients bearing the -1208 insertion allele of tissue factor (TF) and longer glycoprotein Ib-alpha (GpIbalpha) variants may come to surgical attention sooner and undergo coronary artery bypass grafting (CABG) at a younger age. The authors tested this hypothesis in a cardiac surgery population.

Methods

The impact of the number of TF -1208 insertion alleles and the number of GpIbalpha repeats on age at first CABG were tested in 424 elective coronary bypass patients. Multivariate regression included traditional risk factors of sex, hypertension, diabetes, hyperlipidemia, and smoking. The authors also tested the hypothesis that these alleles are correlated with age at first noncoronary cardiac surgery in a group of 143 patients undergoing noncoronary cardiac operations.

Result

Both the number of TF -1208 insertion alleles and total number of GpIbalpha repeats were associated with younger age at first CABG in a univariate analysis. In multivariate regression in which traditional risk factors were included, the number of TF -1208 insertion alleles and the total number of GpIbalpha repeats were independent contributors toward age at first CABG. Neither polymorphism had a significant impact on age at first noncoronary cardiac surgery.

Conclusions

Genetic variants in TF and GpIbalpha are associated with younger age at first CABG, indicating that the younger and older first-time CABG populations are different on the genetic level. How these genetic differences may account for age-associated differences in perioperative risk will be the subject of future investigations.
Acid-induced Lung Injury
Authors: Madjdpour Lilly , Kneller Sita , Booy Christa , Pasch Thomas , Schimmer Ralph C. , Beck-Schimmer Beatrice
Published: November 2003

Background

Aspiration of acidic gastric contents leads to acute lung injury and is still one of the most common clinical events associated with acute lung injury. This study was performed to assess acid-induced lung inflammation in vitro and in vivo with respect to the time pattern of activated transcription factor nuclear factor-kappaB (NF-kappaB) and proinflammatory molecules.

Methods

L2 cells (alveolar epithelial cells) were exposed for various periods to a medium with a pH of 6. In the in vivo model, 1 ml/kg of 0.1 n acidic solution was instilled into the lungs of rats. NF-kappaB binding activity and expression pattern of inflammatory mediators were determined. Blocking studies were performed with the NF-kappaB inhibitor pyrrolidine dithiocarbamate.

Results

In vitro NF-kappaB binding activity showed a biphasic expression pattern with a first peak at 1 h and a second one at 6-8 h. In acid-injured rat lungs, NF-kappaB binding activity was confirmed in a biphasic manner with a first increase at 0.5-2 h (608 +/- 93% and 500 +/- 15%, respectively, P < 0.05) and a second peak at 8 h (697 +/- 35% increase, P < 0.005). Whole lung mRNA for macrophage inflammatory protein-1beta and macrophage inflammatory protein-2 showed a similar expression pattern, which could explain the biphasic neutrophil recruitment. Intratracheal pyrrolidine dithiocarbamate attenuated lung injury as evidenced by a reduction of neutrophil accumulation and expression of inflammatory mediators.

Conclusions

These data suggest that NF-kappaB binding activity plays a key role in molecular and cellular events in acid-induced lung injury.
Development of Neuropathic Pain in the Rat Spared Nerve Injury Model Is Not Prevented by a Peripheral Nerve Block
Authors: Suter Marc R. , Papaloïzos Michael , Berde Charles B. , Woolf Clifford J. , Gilliard Nicolas , Spahn Donat R. , Decosterd Isabelle
Published: November 2003

Background

The mechanisms responsible for initiation of persistent neuropathic pain after peripheral nerve injury are unclear. One hypothesis is that injury discharge and early ectopic discharges in injured nerves produce activity-dependent irreversible changes in the central nervous system. The aim of this study was to determine whether blockade of peripheral discharge by blocking nerve conduction before and 1 week after nerve injury could prevent the development and persistence of neuropathic pain-like behavior in the spared nerve injury model.

Methods

Bupivacaine-loaded biodegradable microspheres embedded in fibrin glue were placed in a silicone tube around the sciatic nerve to produce a conduction block. After sensory-motor testing of block efficacy, a spared nerve injury procedure was performed. Development of neuropathic pain behavior was assessed for 4 weeks by withdrawal responses to stimulation (i.e., von Frey filaments, acetone, pinprick, radiant heat) in bupivacaine microspheres-treated animals (n = 12) and in controls (n = 11).

Results

Bupivacaine microspheres treatment produced conduction blockade with a complete lack of sensory responsiveness in the sural territory for 6 to 10 days. Once the block wore off, the degree of hypersensitivity to stimuli was similar in both groups.

Conclusions

Peripheral long-term nerve blockade has no detectable effect on the development of allodynia or hyperalgesia in the spared nerve injury model. It is unlikely that injury discharge at the time of nerve damage or the early onset of ectopic discharges arising from the injury site contributes significantly to the persistence of stimulus-evoked neuropathic pain in this model.
Antinociceptive Effect of Morphine, but not μ Opioid Receptor Number, Is Attenuated in the Spinal Cord of Diabetic Rats
Authors: Chen Shao-Rui , Pan Hui-Lin
Published: November 2003

Background

The mechanisms of decreased analgesic potency of mu opioids in diabetic neuropathic pain are not fully known. The authors recently found that G protein activation stimulated by the mu opioid agonist is significantly reduced in the spinal cord dorsal horn in diabetes. In the current study, they determined potential changes in the number and binding affinity of mu opioid receptors in the spinal cord in diabetic rats.

Methods

Rats were rendered diabetic with an intraperitoneal injection of streptozotocin. The nociceptive withdrawal threshold was measured before and after intrathecal injection of morphine by applying a noxious pressure stimulus to the hind paw. The mu opioid receptor was determined with immunocytochemistry labeling and a specific mu opioid receptor radioligand, [3H]-(D-Ala2,N-Me-Phe4,Gly-ol5)-enkephalin ([3H]-DAMGO), in the dorsal spinal cord obtained from age-matched normal and diabetic rats 4 weeks after streptozotocin treatment.

Results

The antinociceptive effect of intrathecal morphine (2-10 microg) was significantly reduced in diabetic rats, with an ED50 about twofold higher than that in normal rats. However, both the dissociation constant (3.99 +/- 0.22 vs. 4.01 +/- 0.23 nm) and the maximal specific binding (352.78 +/- 37.26 vs. 346.88 +/- 35.23 fmol/mg protein) of [3H]-DAMGO spinal membrane bindings were not significantly different between normal and diabetic rats. The mu opioid receptor immunoreactivity in the spinal cord dorsal horn also was similar in normal and diabetic rats.

Conclusions

The reduced analgesic effect of intrathecal morphine in diabetes is probably due to impairment of mu opioid receptor-G protein coupling rather than reduction in mu opioid receptor number in the spinal cord dorsal horn.
Value of Videostroboscopic Parameters in Differentiating True Vocal Fold Cysts From Polyps
Authors: Shohet Jack A. , Courey Mark S. , Scott Margie A. , Ossoff Robert H.
Published: November 2003

Differentiating between benign true vocal fold (TVF) cysts, polyps, and nodules on the basis of their gross appearance would be advantageous in determining the need for surgical therapy. A retrospective study of 32 patients covering 31 months was done to assess the ability to differentiate these lesions on the basis of stroboscopic parameters. Stroboscopic examinations were evaluated for symmetry, amplitude, periodicity, mucosal wave, and closure. Preoperative diagnoses were validated with operative and histologic confirmation.

Mucosal wave was absent or diminished in 100% of TVF cysts and present or increased in 80% of TVF polyps (P<.05). Thirty‐one percent of original histopathologic diagnoses were modified after pertinent clinical information was provided to the pathologist. Therefore, stroboscopic evaluation of mucosal wave is helpful in preoperative differentiation of TVF cysts and polyps, and providing clinical information to the pathologist is critical for useful histologic information.
Surgical Treatment of Acoustic Neuroma (Vestibular Schwannoma) in the United States
Authors: Wiegand David A. , Ojemann Robert G. , Fickel Virginia
Published: November 2003

In 1989, the Acoustic Neuroma Association established a multisurgeon, multi‐institutional registry to collect data related to the treatment of patients with acoustic neuroma. This report analyzes information from the 1579 surgically treated patients who were entered in the registry between January 1, 1989, and February 28, 1994.
Endonasal Endoscopic Surgery for Rhinogen Intraorbital Abscess
Authors: Wolf Stephan R. , Göde Ulrich , Hosemann Werner
Published: November 2003

Intraorbital abscess is a serious complication of sinusitis with the danger of permanent loss of vision and even the danger of life‐threatening progress. The recommended surgical procedure in the literature for drainage of an intraorbital abscess is the external approach. We report on successful functional endonasal endoscopic surgery in a series of six sequential cases with intraorbital abscesses following sinusitis. The main advantages of this approach are the simultaneous treatment of causative disorders with surgery following the pathogenic route of the abscess formation and lack of trauma to further structures. The endoscope with 25‐ or 70‐degree angled axis of vision enables the surgeon to explore and drain the abscess cavity, which often is located behind the bulbus, with minimal trauma. For the trained surgeon the field of vision is favorable as compared with the external approach when the abscess is located right in the axis of vision and one has to cut through healthy tissue and the intact skin, which, especially in children, can lead to long‐lasting visible scars.
Endoscopic Dacryocystorhinostomy
Authors: Sprekelsen Manuel Bernal , Barberán Manuel Tomás
Published: November 2003

Endoscopic dacryocystorhinostomy represents a new and promising approach to obstruction of lacrimal pathways. The surgical technique is described in detail. The results of 152 procedures were good or very good in 96% of cases, and no major complications occurred.
Expression of Growth Factors, Proto‐oncogenes, and p53 in Nasopharyngeal Angiofibromas
Authors: Nagai M. A. , Butugan O. , Logullo A. , Brentani M. M.
Published: November 2003

Biopsies from 25 juvenile nasopharyngeal angiofibromas (JNAs) and respective normal inferior turbinates were examined and compared. The expression patterns of the messenger RNAs (mRNAs) for various growth factors possibly involved in the growth of mesenchymal cells, as well as angiogenesis and fibrosis, were also compared. These growth factors included insulin‐like growth factor II (IGF‐II), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factors‐β1(TGF‐β1) and platelet‐derived growth factors (PDGF‐A and PDGF‐B). Quantification of mRNA coding for proto‐oncogenes and suppressor genes related to proliferation (i.e.,c‐myc,c‐fos,p53) was also undertaken.

Tumor and turbinates expressed similar levels of bFGF, VEGF, TGF‐β1, c‐myc,c‐fos,and PDGF‐A mRNAs. The presence of TGF‐β1protein was confirmed by immunohistochemistry in several structures that characterize the lesions of JNA, which suggests that TGF‐β1may play a role in the development of the fibrous component of this tumor. PDGF‐B and p53 were overexpressed (i.e.,twice the mean level found in turbinates) in 50% and 32% of JNAs, respectively, but there was no statistical significance when compared with controls. Statistically significant increased expression of IGF‐II mRNA was observed in JNA (P=.04). IGF‐II mRNA levels were correlated to p53 (P=.05) and PDGF‐B (P=.034), indicating a possible synergistic action of such factors in JNA. The results of this study suggest that IGF‐II might be a potential growth regulator of nasopharyngeal angiofibromas.
Guinea Pig Inner Ear Antigens
Authors: Cao M. Y. , Deggouj N. , Gersdorff M. , Tomasi J.‐P.
Published: November 2003

In this study, the authors attempted to develop a method of extracting guinea pig inner ear antigens for otoimmunological research, and to investigate the distribution of the antigens in the various structures of the inner ear. The antigens were extracted either from the entire or from various parts of the guinea pig inner ear. These antigens were separated on sodium dodecylsulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) gels. Western blot techniques were nsed to test sera from patients with inner ear disease against guinea pig inner ear protein extraets. It was found that the various molecular weight antigens in the inner ear were associated with the different structures of the inner ear. The sera of 37.5% N=80) of patients reacted with two bands (30 and 58 kd) of the guinea pig inner ear immunoblots. The 58‐kd band was not specific to the inner ear, but instead was also found in the immunoblots of other guinea pig tissues (brain, lung, and liver). This study suggests that the various antigens of interest could be further extracted and purified from the corresponding locations of the inner ear.
Speech and Swallowing Rehabilitation Following Devastating Caustic Ingestion: Techniques and Indicators for Success
Authors: Shikowitz Mark J. , Levy Joan , Villano Dorothy , Graver L. Michael , Pochaczevsky Rubem
Published: November 2003

Caustic material ingestion, either accidental or intentional, may result in tissue and organ destruction leading to a wide range of complications, including loss of speech and the ability to eat. The esophagus can be reconstructed successfully, but reopening the larynx and upper airway poses a significant therapeutic dilemma. External reconstruction may put the neoesophagus at risk. Loss of the normal swallowing mechanism and the protective supraglottic structures often results in fatal aspiration.

The authors present three cases of successful endoscopic laser recannulation of the larynx with esophageal replacement. The discussion includes surgical technique and the tools used to determine the success of the reconstruction, including computed tomographic scanning, modified barium swallow, placement of an upper esophageal anastomosis, psychologic support, and speech and swallowing therapy.
Intratemporal Facial Nerve Perineurioma
Authors: Li Daqing , Schauble Barbara , Moll Carl , Fisch Ugo
Published: November 2003

Forty‐two cases of perineurioma have been reported in the literature. This report adds the first intratemporal facial nerve perineurioma to the literature and reviews the others. Unlike schwannoma and neurofibroma, the histological features of perineurioma demonstrate onion bulb‐like structures with a strong positive immunoreactivity for epithelial membrane antigen. The clinical history of gradual facial nerve paresis was 15 years in this case presentation and the clinical diagnosis of tumor was overlooked.
Structural Characterization of Persistent Tympanic Membrane Perforations in Man
Authors: Spandow Odd , Hellström Sten , Dahlström Michael
Published: November 2003

In the present structural study the authors investigated the border of permanent tympanic membrane (TM) perforations in patients selected for myringoplasty. Furthermore, a panel of monoclonal antibody markers that recognize different epitopes within glycosaminoglycans as well as antibodies to epidermal growth factor and fibronectin were applied to the sections. In half of the specimens the epithelial junction ended at the inside of the perforation border, whereas in the other half it was located at the perforation border itself. In the junctional area the keratinocytes were covered by a thick keratin layer which protruded as a spur centripetally in order to bridge the perforation. Epidermal cells formed papillae and contained remnants of keratinocyte nuclei that showed similarities to those of the skin in inflammatory conditions. The connective tissue layer was fibrous and showed areas containing sclerotic plaques. The inner epithelium of the TM had abundant ciliae, thus supporting the concept that cells of the mucosal lining of the TM are able to differentiate in inflammatory conditions into ciliated cells and secretory cells. The immunoreactivity of hyaluronan and other glycosaminoglycans, the immunoreactivity of epidermal growth factor, and the immunoreactivity of fibronectin, all of which are known to occur in healing wounds, were only scantily demonstrated; this could be one reason for the arrested healing and a reason why the natural drive to complete a mature closure is abandoned.
The Stylomastoid Area: Anatomic‐Histologic Study and Surgical Approach
Authors: Holt James J.
Published: November 2003

This three‐part study explored the difficult problem of dissecting the facial nerve through the soft tissues of the mastoid tip. The anatomic relationships of the mastoid tip tissues were measured in 20 specimens. At the stylomastoid foramen, the facial nerve lies an average of 9 mm from the digastric muscle, 11 mm from the external canal, and 21 mm from the nerve's parotid bifurcation. The histologic relationships between the nerve sheath and the mastoid tip fascial tissues were examined in 10 specimens. The tight adherence of sheath and fascial fibers prevent their easy separation. By applying this new anatomic and histologic knowledge on cadaver specimens, the author refined a technique for the safe dissection of the facial nerve through mastoid tip tissues. This technique has proven successful in the operating room.
Ototoxicity Resulting From Combined Administration of Cisplatin and Gentamicin
Authors: Riggs Landon C. , Brummett Robert E. , Guitjens Sydney K. , Matz Gregory J.
Published: November 2003

The hypothesis that cisplatin can augment the ototoxicity of gentamicin was tested. Seven groups of 11 guinea pigs each were given a single dose of cisplatin either alone or 14 days before, at the beginning, midway through, or at the end of a course of gentamicin administered daily for 14 days. Blood and perilymph gentamicin and cisplatin concentrations were determined in three of the animals from each group. Auditory damage was determined in the remaining 8 animals electrophysiologically by measuring the compound action potential and alternating‐current cochlear potential. Hair cell damage was determined using the surface preparation technique. An augmented ototoxic effect occurred when the cisplatin was given early in the 14‐day course of gentamicin and did not occur when it was given at the end of treatment.
Identifying Obstructive Sleep Apnea in Patients Presenting for Laser‐Assisted Uvulopalatoplasty
Authors: Vaidya Abhay M. , Petruzzelli Guy J. , Walker Regina Paloyan , McGee Daniel , Gopalsami Chellam
Published: November 2003

The authors report on a series of 850 patients with snoring who were evaluated for laser‐assisted uvulopalatoplasty (LAUP). Stepwise multivariate linear regression was employed to correlate patient symptoms and characteristics to the respiratory disturbance index (RDI). Body mass index, falling asleep while driving, snoring every night, and stopping breathing during sleep were found to correlate strongly with an increasing RDI (variance of 25%). Logistic multivariate linear regression analysis was used to predict the outcome of apnea (RDI>10). This model selected all of the above variables, as well as age, male sex, and the total number of symptoms, as being strong predictors of apnea. A receiver operating characteristic curve was used to describe the ability of this model to predict apnea.

The authors conclude that otolaryngologists play an important role in the evaluation of OSAS, especially when a snoring patient may undergo LAUP, and they present an algorithm for the evaluation of such a patient. The authors believe that the clinical assesment, including a thorough history and a complete physical examination, remains extremely important in this evaluation. At present, the authors strongly recommend referral for a PSG if there is any suspicion of OSAS.
Hypericin: A New Laser Phototargeting Agent for Human Cancer Cells
Authors: VanderWerf Quinten M. , Saxton Romaine E. , Chang Andrew , Horton Dennis , Paiva Marcos B. , Anderson Jamey , Foote Christopher , Soudant Jacques , Mathey Annick , Castro Dan J.
Published: November 2003

Laser activation of anthracycline‐related drugs combines chemotherapy with photoablation for improved treatment. Hypericin, a structurally related anthraquinone, was tested for laser activation and cytotoxicity in human cancer cells. Viability of P3 squamous cell carcinoma cells incubated with 1 to 20μg/mL hypericin was reduced by more than 95% after 1 minute exposure at 4°C to an argon laser (514 nm, 5 W), a KTP‐532 laser (532 nm, 5 W), or a 20‐A xenon lamp. Viability was reduced over 90% in six human carcinoma, sarcoma, and melanoma cell lines by this combined treatment, but only trace toxicity was seen after separate exposure to hypericin or light alone. These results show that hypericin is a sensitive agent for phototherapy of human cancer cells in vitro and indicate that this drug may be useful for tumor targeting via minimally invasive imaging‐guided laser fiberoptics.
Supracricoid Partial Laryngectomy After Failed Laryngeal Radiation Therapy
Authors: Laccourreye Ollivier , Weinstein Gregory , Naudo Philippe , Cauchois Régis , Laccourreye Henri , Brasnu Daniel
Published: November 2003

Twelve patients managed with supracricoid partial laryngectomies(SCPLs) after failed laryngeal radiation therapy (RT) were evaluated. None of the recurrent tumors were amenable to vertical or horizontal partial laryngectomy. Results were analyzed for tracheostomy decannulation, oral alimentation, morbidity, local control, and survival. Major complications included perichondritis (2 patients), laryngeal stenosis (2 patients), and pneumonia from aspiration (1 patient). Mucocutaneous fistula and cricoarytenoid joint ankylosis were not encountered. Margins of resection were uninvolved in all cases. The Kaplan‐Meier 3‐year actuarial survival and local control estimate was 83.3%. Salvage total laryngectomy allowed for an overall 100% local control rate and a 75% laryngeal preservation rate.

This preliminary report suggests that, in patients with failed laryngeal RT not amenable to vertical or horizontal partial laryngectomy, the SCPL procedures should be discussed before advocating salvage total laryngectomy. Further series analyzing the role and limitations of the various SCPL procedures after failed laryngeal RT are warranted.
Management of Carcinoma of the Supraglottic Larynx: Evolution, Current Concepts, and Future Trends
Authors: Myers Eugene N. , Alvi Aijaz
Published: November 2003

The treatment of cancer of the supraglottic larynx has undergone an evolution. Better understanding of the anatomy and biology of cancer in this anatomic site has enabled surgeons to devise effective oncologic strategies while making every effort to preserve the function of the larynx. Certain recent concepts and changing trends have emerged in the treatment of cancer of the supraglottic larynx, including the treatment of the neck, significance of extracapsular spread of tumor in cervical lymph nodes, and conservation laser surgery. In 1985, Snyderman et al.1 reported the prognostic significance of extracapsular spread in patients with cancer of the supraglottic larynx. In 1990, Lutz et al.2 reported the results of our experience with the treatment of 202 patients. The review verified the significant risk of bilateral neck disease in these patients, even with adjuvant radiation therapy. Accordingly, since 1990 all patients having cancer of the supraglottic larynx have been treated in the Department of Otolaryngology at the University of Pittsburgh with bilateral neck dissections. The use of adjuvant radiation therapy has been based on the presence of extracapsular spread. This study documents the oncologic effectiveness of this treatment and confirms the efficacy of bilateral neck dissections in an attempt to control neck disease and the prognostic significance of extracapsular spread. We review the evolution of the treatment of cancer of the supraglottic larynx, present our results, and consider innovative surgical approaches.

Laryngoscope, 106:559‐567, 1996
Longitudinal Evaluation of Vocal Function After Thyroplasty Type I in the Treatment of Unilateral Vocal Paralysis
Authors: Lu Fang‐Ling , Casiano Roy R. , Lundy Donna S. , Xue Jun‐Wu
Published: November 2003

This study investigated longitudinal changes of vocal efficiency and stability after primary thyroplasty type I. Fifty‐three patients with unilateral vocal‐fold paralysis underwent vocal‐function evaluation preoperatively and at periodic intervals of 1, 3, and 6 months postoperatively. Vocal‐function assessment included videostrobolaryngoscopic examination, acoustical and aerodynamic analysis, and perceptual judgment of voice characteristics. Parameters that included glottic‐gap size, maximum phonation time, glottic‐flow rate, jitter, harmonic/noise ratio, breathiness, hoarseness, loudness, and phrasing showed significant improvement after thyroplasty and remained stable as early as 1 month postoperatively, with only slight fluctuations over a 6‐month period. Postoperative voice outcome was not affected by age, sex, duration of vocal symptoms, cause of paralysis, or preoperative pulmonary function.

Laryngoscope, 106:573‐577, 1996
Development of the Facial Recess: Implications for Cochlear Implantation
Authors: Eby Thomas L.
Published: November 2003

More attention is being focused on the growth and development of the facial recess because of the use of cochlear implantation in children over 2 years of age and the prospect of using implants in even younger children. The facial recess and the extended facial recess were measured in 123 temporal bones from 73 individuals ranging in age from 8 weeks in utero to 7 years after birth. The goals were to trace the development of the facial recess and to determine whether this area continues to grow into childhood.

The facial recess enlarges throughout fetal life with the development of the facial canal and the tympanic annulus. Reichert's cartilage, seen early in utero in the facial recess, gradually resorbs but may persist in the newborn. In full‐term infants, the facial recess reaches 3.25 mm at the oval window and 2.62 mm at the round window. The extended facial recess reaches 3.79 mm at the oval window and 3.04 mm at the round window. No statistically significant growth of the facial recess after birth could be demonstrated in this study. The data suggest that the facial recess is probably adult sized at birth and should allow surgical access for cochlear implantation in very young children.

Laryngoscope, 106 (Suppl. 80):1‐7, 1996
Prevalence and Assessment of Qualitative Olfactory Dysfunction in Different Age Groups
Authors: Nordin Steven , Murphy Claire , Davidson Terence M. , Quiñonez Carlo , Jalowayski Alfredo A. , Ellison Dennard W.
Published: November 2003

The prevalence of parosmia and phantosmia among 363 chemosensory and nasal/sinus patients was studied, as was the accuracy with which our clinical questionnaire could assess these dysfunctions. We then investigated whether patients with parosmia or phantosmia, matched for odor intensity, perform poorer on odor identification than do patients with no dysosmia. More than 40% of the study group evidenced either parosmia (18.7%) and/or phantosmia (25.6%), a finding that suggests that more attention should be paid by the medical practitioner in addressing qualitative olfactory dysfunction. Furthermore, it appears that assessment of these dysfunctions may aid in differential diagnosis, and that questionnaires can be used with reasonable validity irrespective of the patient's age. Finally, the results imply that parosmia may be reflected in a discrepancy between odor identification and detection.
Characteristics of an In Vivo Canine Model of Phonation With a Constant Air Pressure Source
Authors: Nasri Sina , Namazie Ali , Ye Ming , Kreiman Jody , Gerratt Bruce R. , Berke Gerald S.
Published: November 2003

Many previous studies of laryngeal biomechanics using in vivo models have employed a constant air flow source. Several authors have recently suggested that the lung‐thorax system functions as a constant pressure source during phonation. This study describes an in vivo canine system designed to maintain a constant peak subglottic pressure (Psub) using a pressure‐controlling mechanism.

Increasing levels of recurrent laryngeal nerve (RLN) stimulation resulted in a significant rise in resistance followed by a plateau. For a given Psub, flow decreased significantly and precipitously with increasing stimulation and then quickly plateaued. Vocal intensity increased with increasing RLN stimulation until a peak was reached. After this peak, intensity dropped until a plateau was reached, corresponding to the flow minimum. At a given Psub, increasing levels of RLN stimulation resulted in a normal distribution of vocal efficiencies.
Orbicularis Oris Muscle Injury in Brass Players
Authors: Papsin Blake C. , Maaske Laura A. , McGrail J. Simon
Published: November 2003

The embouchure of the brass player is critical to tone production and largely depends on the integrity of the orbicularis oris muscle. Injury to this muscle can cripple the professional musician by causing fatigue, pain, and tonal deterioration. Ten brass players presented with muscular defects in the orbicularis oris muscle. Examination identified areas of abnormality within the muscle and electromyography (EMG) ruled out a neurologic deficit. All patients underwent exploration under neuroleptic anesthesia, and 9 patients underwent repair. The technique is described. The repaired patients reported improvement after the operation and all resumed playing at their premorbid level. The 10th patient was found to have thinning of the entire orbicularis oris muscle (presumably congenital) and was not able to be repaired. There were no complications of the procedure and no recurrences.
Immunobiological Peculiarities of Cholesteatoma in Children: Quantification of Epithelial Proliferation by MIB 1
Authors: Bujía Jesús , Holly Anja , Antolí‐Candela Francisco , Tapia Mario Guzman , Kastenbauer Ernst
Published: November 2003

Cholesteatoma in children is characterized by a more extensive and rapid growth in the middle ear and mastoid cavities. The growth characteristics of the cholesteatoma in 20 children were studied using the monoclonal antibody MIB 1, which recognizes a nuclear antigen expressed by cells in the G1, S, and G2/M phases. Specimens of normal adult auditory meatal skin (n = 15) and adult cholesteatoma (n = 15) served as controls. The tissue specimens were prepared for immunohistochemical examination using the alkaline phosphatase‐antialkaline phosphatase method and an automatic image analyzer. Specimens of normal skin revealed an average MIB 1 score of 9.2 ± 3.1%. Child and adult cholesteatomas showed higher values. The average MIB 1 score was higher in child cholesteatoma (42 ± 9.4%) than in adult cholesteatoma (28.2± 6%). This difference was statistically significant (P<.01). Our results confirm a significant increase of the proliferative rate of cholesteatoma keratinocytes in children, giving an explanation for the more aggressive clinical behavior observed in these patients.

Laryngoscope, 106:865‐868, 1996
Prognostic Value of EGFR and TGF‐α in Early Laryngeal Cancer Treated With Radiotherapy
Authors: Wen Qing‐Hua , Miwa Takaki , Yoshizaki Tomokazu , Nagayama Ikuo , Furukawa Mitruru , Nishijima Hiroshi
Published: November 2003

The purpose of this study was to determine the overexpression of both epidermal growth factor receptor (EGFR) and transforming growth factoralpha(TGF‐α) (a ligand of EGFR) in early laryngeal squamous cell carcinoma. In addition, we attempted to evaluate the prognostic values of our findings.

Expression of EGFR and TGF‐α in tumor tissue was examined immunohistochemically in 68 patients who had been treated with radiotherapy for early laryngeal cancer. Overexpression of the two factors was noted in 42.6% and 55.9%, respectively. No significant differences due to age, tumor size, and location or grade of cancer tissues were seen.

Higher survival rates, found in patients with EGFR (‐) and TGF‐α (‐) tumors as compared with those with EGFR (+) and TGF‐α (+) (97.4%, 100% and 86.2%, 86.8%, respectively), were not statistically significant. The recurrence rates were similar between EGFR (+) and EGFR (‐) (37.9% and 35.9%, respectively). However, the recurrence rate in patients with TGF‐α (+) was significantly higher (57.9%) than in those with TGF‐α (‐) (10%; P<.01). Therefore overexpression of TGF‐α may be an important indicator for recurrence in patients with early laryngeal squamous cell carcinoma treated by irradiation.

Laryngoscope, 106:884‐885, 1996
Microbiology of Subperiosteal Orbital Abscess and Associated Maxillary Sinusitis
Authors: Brook Itzhak , Frazier Edith H.
Published: November 2003

Aspirate of pus from eight subperiosteal orbital abscesses (SPOAs) and their corresponding infected sinuses were studied for aerobic and anaerobic bacteria. Polymicrobial flora was found in all instances, and the number of isolates varied from two to five. Anaerobes were recovered from all specimens. The predominant isolates were Peptostreptococcus spp,Prevotella spp, Fusobacterium spp,Staphylococcus aureus, and microaerophilic streptococci. Concordance in the microbiological findings between SPOA and the infected sinus was found in all instances. However, certain organisms were only present at one site and not the other. Fourteen β‐lactamase‐producing organisms were present in nine specimens. These data confirm the importance of anaerobic bacteria in sinusitis and demonstrate their predominance in the associated SPOA.
Immunohistochemical Localization of Nitric Oxide Synthase Activity in Upper Respiratory Epithelium
Authors: Rosbe Kristina W. , Mims James W. , Prazma Jiri , Petrusz Peter , Rose Austin , Drake Amelia F.
Published: November 2003

Nitric oxide (NO) production in the respiratory epithelium of the upper airways has recently been described. To better delineate the role of epithelial NO, the authors of this study attempted to identify the cell type responsible for the production of NO in rat tracheal epithelium and human nasal epithelium. They localized the activity of NO through immunohistochemical analysis with an antibody to L‐citrulline, a marker for activity of the L‐arginine‐dependent nitric oxide synthase (NOS) pathway. Using anti‐inducible NOS (iNOS) and anti‐constitutive NOS (cNOS) antibodies, they also attempted to identify the specific NO isotypes that were present.

The tracheal and nasal epithelium demonstrated strong immunoreactivity to citrulline in ciliated cells. The ciliated cells of the nasal turbinates demonstrated strong iNOS positivity, but no significant cNOS immunoreactivity. The study findings that iNOS activity is present in ciliated epithelial cells of rat and human upper respiratory epithelium suggest that NO may play a role in epithelial homeostasis and could potentially play a role in the pathogenesis of mucociliary dysfunction.
Evaluation of the Vestibular System by Magnetic Resonance Angiography
Authors: Welsh Louis W. , Welsh John J. , Jaffe Stephen C. , Healy Michael P.
Published: November 2003

This report describes the normal arterial patterns of the vestibulocerebellar regions visualized by magnetic resonance angiography. Variations in the vertebrobasilar arterial system are described, limitations in imaging are discussed, and collateral connections within the cerebellar vessels and the circle of Willis are reviewed. Clinical correlations are defined between the vestibular nuclei, the associated intra‐axial tracts, and with specific posterior cerebral and brain stem arteries.