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Animal Study (animal + study)
Kinds of Animal Study Selected AbstractsDETECTION OF PERIVASCULAR BLOOD FLOW IN VIVO BY CONTRAST-ENHANCED INTRACORONARY ULTRASONOGRAPHY AND IMAGE ANALYSIS: AN ANIMAL STUDYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2007Manolis Vavuranakis SUMMARY 1Acute coronary syndromes are mostly the result of coronary plaque rupture. Diagnostic techniques focusing on the early detection of those plaques that are prone to rupture are still limited. Increased neovascularization in the adventitia and within the atherosclerotic plaque have recently been identified as common features of inflammation and plaque vulnerability. Contrast-enhanced intravascular imaging with microbubbles can be used to trace perfusion. 2In the present study, we examined the perivascular network of the left anterior descending coronary arteries and left circumflex arteries of four domestic, clinically healthy pigs using intracoronary ultrasound after injection of microbubbles with a differential imaging technique (ACESÔ; Computational Biomedicine Laboratory, University of Houston, Houston, TX, USA). Our aim was to detect blood flow into the coronary lumen and perivascular flow in contrast-enhanced images. Eleven regions of interest (ROI), including perivascular structures, were compared with regard to their grey scale level before and after the injection of SonoVue® (0.06 mL/kg; Bracco Diagnostics, Princeton, NJ, USA). 3A statistically significant (P = 0.018) enhancement was found in the echogenicity of the total perivascular space (adventitial region and perivascular vessels), as indicated by an increase in grey level intensity from 8.33 ± 0.80 (before) to 10.11 ± 0.88 (after microbubble injection). A significant enhancement of the 11 selected ROI (perivascular structures) was also recorded after the injection of microbubbles (from 7.92 ± 2.14 to 14.03 ± 2.44; P = 0.008). 4We believe that the detection of perivascular structures with contrast-enhanced intracoronary ultrasonography combined with proper image processing may reinforce our future efforts in the detection of vasa vasorum, an active participant in the creation of acute coronary events. [source] An Animal Study of a Newly Developed Skin-Penetrating Pad and Covering Material for Catheters to Prevent Exit-Site Infection in Continuous Ambulatory Peritoneal DialysisARTIFICIAL ORGANS, Issue 12 2009Masato Aoyama Abstract Because currently available peritoneal dialysis catheters are not sufficiently biocompatible with the skin and subcutaneous tissue at the site of penetration, exit-site infection due to pericatheter pocket formation caused by epidermal downgrowth over a long period of time has increasingly become a problem. We developed a new, biocompatible, segmented polyurethane porous material and devised a novel skin-penetrating pad, the form and material of which we optimized for application in peritoneal dialysis catheters. For the extent of tissue ingrowth into this porous material to be examined, test materials with different pore diameters were inserted into hollow silicone tubes and implanted in the subcutaneous tissue of a goat. Four weeks later, the tubes were extracted, and, after the extent of granulation tissue ingrowth was measured, histopathological evaluation was made. Our novel skin-penetrating pad has three disklike layers of the segmented polyurethane material with different pore sizes, into the center of which a polyurethane catheter is inserted. These pads were implanted in the skin of a goat and clinically observed over a 2-year period, after which they were extracted and histopathologically analyzed. In accordance with actual clinical procedures, a commercial CAPD catheter equipped with our skin-penetrating pad was left indwelling in a goat for 4 months, and the performance of the pad was evaluated after repeated periodic infusion and drainage of the dialysate in and out of the abdominal cavity. There was no inflammation of the ingrown tissue in the pores of the segmented polyurethane material as well as the surrounding tissue, which indicated favorable tissue biocompatibility. The extent of tissue ingrowth was greater as the pore size of the material was larger, and the tissue tended to be mature, mainly consisting of collagenous fibers. The skin-penetrating pad using the porous material, of which tissue ingrowth was thus optimized, tightly adhered to the goat skin throughout the 2-year experimental period without any special wound care such as cleansing or disinfection. The performance of the skin-penetrating pad was similarly favorable when attached to a commercial continuous ambulatory peritoneal dialysis catheter. The newly developed segmented polyurethane porous material had excellent tissue biocompatibility and tissue ingrowth. The skin-penetrating pad devised by using this porous material did not cause epidermal downgrowth, suggesting that it may be effective for the prevention of exit-site infection. [source] Tissue-engineered trachea for airway reconstruction,THE LARYNGOSCOPE, Issue 11 2009Mark Weidenbecher MD Abstract Objectives/Hypothesis: Scaffold-free cartilage has been used to engineer biocompatible and mechanically stable neotracheas in vivo. The purpose of this animal study was to determine if neotracheal constructs, implanted paratracheally, could successfully be used for segmental tracheal reconstruction. Study Design: Animal study. Methods: Culture-expanded auricular rabbit chondrocytes were used to engineer scaffold-free cartilage sheets. Cartilage and a strap muscle flap were wrapped around a tube and implanted paratracheally. At 12 to 14 weeks postimplantation neotracheas were used to reconstruct 20 mm tracheal defects. Surgical technique was modified several times in an attempt to decrease the amount of neotracheal obstruction and fibrosis. In one of the six rabbits, neotrachea with its intact strap muscle flap was dropped into the defect followed by an end-to-end anastomosis; in two animals the muscle flap was partially, and in one rabbit completely removed. In two animals the muscle flap was partially removed, the tube reinserted, and the construct reimplanted for 5 weeks to allow formation of a fibrous lining over the exposed cartilage followed by tracheal reconstruction. Results: All implants developed into vascularized and mechanically sound neotracheas. Following reconstruction, none of the animals showed immediate signs of respiratory distress; however, one died after 24 hours due to extensive endotracheal muscle flap edema, whereas rabbits who had undergone partial or complete muscle flap removal survived up to 39 days before developing cicatricial stenosis. Conclusions: Tissue-engineered neotracheas proved to have excellent biocompatibility and stability to function under physiologic conditions, but lacked adequate endotracheal lining resulting in neotracheal stenosis. Laryngoscope, 2009 [source] A Novel Drug Therapy for Recurrent Laryngeal Nerve Injury Using T-588,THE LARYNGOSCOPE, Issue 7 2007Yuko Mori MD Abstract Objectives/Hypothesis: We have previously shown that gene therapy using Insulin-like growth factor (IGF)-I, glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), or a combination of these trophic factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy. However, there remain some difficulties preventing this option from becoming a common clinical therapy for RLN injury. Thus, we need to develop novel treatment option that overcomes the problems of gene therapy. R(,)-1-(benzothiophen-5-yl)-2-[2-N,N-diethylamino]ethoxy]ethanol hydrochloride (T-588), a synthetic compound, is known to have neuroprotective effects on neural cells. In the present study, the possibility of new drug treatments using T-588 for RLN injury was assessed using rat models. Study Design: Animal study. Methods: Animals were administered T-588 for 4 weeks. The neuroprotective effects of T-588 administration after vagal nerve avulsion and neurofunctional recovery after recurrent laryngeal nerve crush were studied using motoneuron cell counting, evaluation of choline acetyltransferase immunoreactivity, the electrophysiologic examination, and the re-mobilization of the vocal fold. Results: T-588 administration successfully prevented motoneuron loss and ameliorated the choline acetyltransferase immunoreactivity in the ipsilateral nucleus ambiguus after vagal nerve avulsion. Significant improvements of motor nerve conduction velocity of the RLN and vocal fold movement were observed in the treatment group when compared to controls. Conclusion: These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury. [source] Local and systemic effects of intralaryngeal injection of cidofovir in a canine model,THE LARYNGOSCOPE, Issue 11 2003Dinesh K. Chhetri MD Abstract Objective: The safety of intralaryngeal injection of cidofovir remains a concern. Our goal was to evaluate local and systemic effects of intralaryngeal injection of cidofovir. Study Design: Animal study using a canine model. Methods: Two groups of three young beagle dogs (6 vocal folds in each group) were used. Subepithelial vocal fold injections were performed in each group biweekly for 6 months with 0, 2.5, 5, 10, 20, and 37.5 mg cidofovir in a 0.5 mL volume. Direct laryngoscopy was performed at each injection interval. Complete blood cell count and renal parameters were measured at baseline and monthly thereafter. Histopathologic examination of the vocal folds was performed after the 6-month injection period in one group of animals and after an additional 6-month observation period in the second group. Results: Endomysial edema with muscle fiber separation and dose-dependent atrophy and scarring of the vocal folds was present. Onset of atrophy and scarring was observed after 3,7, and 11 injections in the vocal folds injected with 37.5, 20, and 10 mg cidofovir, respectively. After the 6-month observation period, recovery of histologic abnormalities was complete in the low-dose (0, 2.5 mg) vocal folds, near complete in the intermediate-dose (5, 10 mg) vocal folds, and no apparent recovery was seen in the high-dose (20, 37.5 mg) vocal folds. Leukocyte count and renal parameters remained unchanged at up to 4.26 mg/kg body weight of systemic dose of cidofovir. Conclusions: Intralaryngeal cidofovir leads to dose-dependent scarification of the vocal folds that appears irreversible at higher doses. Lower concentrations of this drug should be used in intralesional intralaryngeal use. [source] Intermittent exposure to low-concentration paraphenylenediamine can be equivalent to single, higher-dose exposureCONTACT DERMATITIS, Issue 5 2007Jonathan M. L. White Hair dye allergy is an important and increasingly common cause of allergic contact dermatitis. The role of repeated exposure in elicitation of allergy has not previously been extensively studied. We have therefore compared elicitation between single and intermittent exposure to paraphenylenediamine (PPD). 23 subjects known to be allergic to PPD from positive patch tests were exposed to 0.3% and 0.03% PPD, both in petrolatum and water, for 5 min at the same site every day for up to 8 D. In the same subjects, single exposures were also performed at different sites, from 5 to 40 min. Other experiments exposed rat skin to radiolabelled PPD as one-off application or multiple exposures. There were 8 reactions in the cumulative exposure site using 0.3% PPD in aqueous solution. In 7 of these, there was an exact correlation with reaction to the cumulative time needed for repeat exposures to elicit a reaction and the time needed for a reaction to the single exposure. There were no reactions to 0.03% PPD in water or pet under either type of exposure condition. There was also a positive correlation between grade of original reaction in clinic (+++, ++, +) and appearance/intensity of elicitation reactions. In the animal study, cumulative time and single exposure time sites correlated with regards to retention of radiolabelled substance within the skin. This study therefore demonstrates for the first time that, over the time period tested, the allergenic component of PPD accumulates in the skin. Hence, intermittent exposure to lower concentrations of PPD may be equivalent to higher concentration, one-off exposure. [source] Analysis of endosulfan and its metabolites in rat plasma and selected tissue samples by gas chromatography,mass spectrometryENVIRONMENTAL TOXICOLOGY, Issue 1 2005Melissa P. L. Chan Abstract A method has been developed for the determination of trace levels of ,-endosulfan, ,-endosulfan, endosulfan sulfate, and endosulfan diol in rat plasma and tissue samples. Endosulfan and its metabolites in the plasma samples were extracted with solid-phase extraction Chromabond-end-capped C18 cartridges and analyzed by a Shimadzu QP-5050A gas chromatograph,mass spectrometer (GCMS) with quadrupole detector in selected-ion-monitoring mode. The analysis of endosulfan and its metabolites in liver and kidney samples involved solvent extraction, Florisil solid-phase-extraction cleanup, and quantitation by GCMS. Recovery experiments for the plasma and tissue samples were conducted over concentration ranges of 10,100 ng mL,1 and 100,1000 ng mL,1, respectively. The method was applied to the analysis of trace levels of endosulfan and its metabolites in plasma and tissue samples collected from an animal study. Trace levels of ,-endosulfan and ,-endosulfan in the ranges of undetectable to 3.11 ,g g,1 and undetectable to 1.19 ,g g,1, respectively, were detected in the kidney samples, whereas trace levels of endosulfan sulfate in the range of 0.02,0.22 ,g g,1 were detected in the liver samples of rats. Neither endosulfan nor its metabolites was detected in any of the plasma samples. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 45,52, 2005. [source] Should dynamic parameters for prediction of fluid responsiveness be indexed to the tidal volume?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010S. T. VISTISEN Background: The respiratory variation in the pre-ejection period (,PEP) has been used to predict fluid responsiveness in mechanically ventilated patients. Recently, we modified this parameter (PEPV) and showed that it was a reliable predictor for post-cardiac surgery, mainly paced, patients when moderately low tidal volumes were used. One of the modifications involved tidal volume indexation, which had not been proposed before for dynamic parameters. The aim of the present animal study was to investigate whether indexation to tidal volume should be part of a new definition of dynamic parameters such as the case for our newly proposed PEPV. Methods: Eight prone, anesthetized piglets (23,27 kg) were subjected to a sequence of 25% hypovolemia, normovolemia, and 25% and 50% hypervolemia. At each volemic level, tidal volumes were varied in three steps: 6, 9, and 12 ml/kg. PEP variations (ms) and pulse-pressure variation (PPV) were measured during the three tidal volume steps at each volemic level. Results: PEP variations increased significantly with increasing tidal volume at all volemic levels but 50% hypervolemia and were proportionally related to the tidal volume at normovolemia. PPV increased significantly with increasing tidal volume at all volemic levels and was roughly proportional to the tidal volume at all volemic levels but hypovolemia. Conclusion: Our study indicates that dynamic parameters are improved by indexing to tidal volume. [source] Automated pre-ejection period variation predicts fluid responsiveness in low tidal volume ventilated pigsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010S. T. VISTISEN Introduction: The respiratory variation in the pre-ejection period (,PEP) has been used to predict fluid responsiveness in mechanically ventilated patients. Recently, we automated this parameter and indexed it to tidal volume (PEPV) and showed that it was a reliable predictor for post-cardiac surgery, mainly paced, patients ventilated with low tidal volumes. The aims of the present animal study were to investigate PEPV's ability to predict fluid responsiveness under different fluid loading conditions and natural heart rates during low tidal volume ventilation (6 ml/kg) and to compare the performance of PEPV with other markers of fluid responsiveness. Methods: Eight prone, anesthetized piglets (23,27 kg) ventilated with tidal volumes of 6 ml/kg were subjected to a sequence of 25% hypovolemia, normovolemia, and 25% and 50% hypervolemia. PEPV, ,PEP, pulse pressure variation (PPV), central venous pressure (CVP), and pulmonary artery occlusion pressure (PAOP) were measured before each volume expansion. Results: Sensitivity was 89% and specificity was 93% for PEPV, 78% and 93% for ,PEP, 89% and 100% for PPV, 78% and 93% for CVP, and 89% and 87% for PAOP. Conclusion: PEPV predicts fluid responsiveness in low tidal volume ventilated piglets. [source] Esophageal Luminal Temperature Measurement Underestimates Esophageal Tissue Temperature During Radiofrequency Ablation Within the Canine Left Atrium: Comparison Between 8 mm Tip and Open Irrigation CathetersJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2008JENNIFER E. CUMMINGS M.D. Introduction: Evaluation of luminal temperature during left atrial ablation is used clinically; however, luminal temperature does not necessarily reflect temperature within the esophageal wall and poses a risk of atrioesophageal fistula. This animal study evaluates luminal esophageal temperature and its relation to the temperature of the external esophageal tissue during left atrial lesions using the 8 mm solid tip and the open irrigated tip catheters (OIC). Methods and Results: A thermocouple was secured to the external surface of the esophagus at the level of the left atrium of the dogs. Luminal esophageal temperature was measured using a standard temperature probe. In four randomized dogs, lesions were placed using an 8 mm solid tip ablation catheter. In six randomized dogs, lesions were placed using the 3.5 mm OIC. The average peak esophageal tissue temperature when using the OIC was significantly higher than that of the 8 mm tip catheter (88.6°C ± 15.0°C vs. 62.3°C ± 12.5°C, P < 0.05). Both OIC and 8 mm tip catheter had significantly higher peak tissue temperatures than luminal temperatures (OIC: 88.6°C ± 15.0°C vs 39.7°C ± 0.82°C, P < 0.05) (8 mm: 62.3°C ± 12.5°C vs 39.0 ± 0.5°C, P < 0.05). Both catheters achieved peak temperatures faster in the tissue as compared to the lumen of the esophagus, although the tissue temperature peaked significantly faster for the OIC (OIC: 25 seconds vs 90 seconds, P < 0.05) (8 mm: 63 seconds vs 105 seconds, P < 0.05). Conclusion: Despite the significant difference in actual tissue temperatures, no significant difference was observed in luminal temperatures between the OIC and 8 mm tip catheter. [source] Dynamic Gd-DTPA enhanced MRI as a surrogate marker of angiogenesis in tissue-engineered bladder constructs: A feasibility study in rabbitsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2005Hai-Ling Margaret Cheng PhD Abstract Purpose To evaluate the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess angiogenesis in tissue-engineered bladder constructs in a blinded animal study, and compare different analysis approaches and their correlation with microvessel density (MVD). Materials and Methods Constructs fortified with vascular endothelial growth factor (VEGF) for enhanced vascularity were grafted onto the bladder in nine rabbits. DCE-MRI of Gd-DTPA uptake was performed and analyzed using Tofts' model, the area under the concentration time curve (AUC), and the uptake slope. DCE-MRI parameters were compared to MVD determined with CD31 immunohistochemistry. Results Significantly increased MVD was found in the high VEGF group (20 ng/g of tissue) but not at low VEGF (10 ng/g) (2.3× increase, P = 0.035 vs. 1.1× over control). Enhanced permeability at low VEGF was suggested by elevated Ktrans, but overall correlation to MVD was poor. Significant correlation to MVD was obtained with AUC8min (r = 0.705, P = 0.034). Furthermore, AUC8min provided the most precise discrimination between different VEGF preparations and was the only parameter to show a significant increase (P = 0.0058) consistent with MVD changes at high VEGF. Conclusion Findings support DCE-MRI for evaluating angiogenesis in bladder constructs and suggest vessel changes other than density. Future studies should incorporate larger contrast agents and permeability assessment to devise an optimal DCE-MRI strategy. J. Magn. Reson. Imaging 2005;21:415,423. © 2005 Wiley-Liss, Inc. [source] Temperature controlled burn generation system based on a CO2 laser and a silver halide fiber optic radiometerLASERS IN SURGERY AND MEDICINE, Issue 5 2003Meir Cohen MD Abstract Background and Objectives Experimental animal study of burns is dependent on a reliable burn generation system. Most of the experimental systems used today are unable to produce precise partial thickness burns. This limits the ability to study minor changes associated with burn care. The aim of the study was to develop a method for generating burns with a fixed depth using a CO2 laser burn generation system. Materials and Methods The burn generation system was composed of two components: a burn generation device and a temperature sensing and control system. These components were designed to operate together in order to keep a constant, predetermined skin surface temperature during prolonged burn generation. One hundred thirty-eight spot burns were generated on the back of five shaved 450 g male Wistar rats. The rat skin was exposed to a 70°C for 5,60 seconds. The burned areas were excised and underwent evaluation by hematoxylin-eosin-stained slide microscopy. Results A linear correlation was found between the duration of exposure and the average burn depth (r,=,0.93). This correlation is represented by the equation: burn depth in millimeters,=,0.012×,(duration in seconds of skin exposure at 70°C). Conclusions The fiber-optic-controlled laser burn generation system studied is a reliable tool for creating partial thickness as well as full thickness skin burns in rats. Lasers Surg. Med. 32:413,416, 2003. © 2003 Wiley-Liss, Inc. [source] Systemic steroid reduces long-term hearing loss in experimental pneumococcal meningitis,THE LARYNGOSCOPE, Issue 9 2010Lise Worsøe MD Abstract Objectives/Hypothesis: Sensorineural hearing loss is a common complication of pneumococcal meningitis. Treatment with corticosteroids reduces inflammatory response and may thereby reduce hearing loss. However, both experimental studies and clinical trials investigating the effect of corticosteroids on hearing loss have generated conflicting results. The objective of the present study was to determine whether systemic steroid treatment had an effect on hearing loss and cochlear damage in a rat model of pneumococcal meningitis. Study Design: Controlled animal study of acute bacterial meningitis. Methods: Adult rats were randomly assigned to two experimental treatment groups: a group treated with systemic steroid (n = 13) and a control group treated with saline (n = 13). Treatment was initiated 21 hours after infection and repeated once a day for three days. Hearing loss and cochlear damage were assessed by distortion product otoacoustic emissions (DPOAE), auditory brainstem response (ABR) at 16 kHz, and spiral ganglion neuron density. Results: Fifty-six days after infection, steroid treatment significantly reduced hearing loss assessed by DPOAE (P < .05; Mann-Whitney) and showed a trend toward reducing loss of viable neurons in the spiral ganglion (P = .0513; Mann-Whitney). After pooling data from day 22 with data from day 56, we found that systemic steroid treatment significantly reduced loss of spiral ganglion neurons (P = .0098; Mann-Whitney test). Conclusions: Systemic steroid treatment reduces long-term hearing loss and loss of spiral ganglion neurons in experimental pneumococcal meningitis in adult rats. The findings support a beneficial role of anti-inflammatory agents in reducing hearing loss and cochlear damage in meningitis. Laryngoscope, 2010 [source] Combinatorial treatments enhance recovery following facial nerve crush,,THE LARYNGOSCOPE, Issue 8 2010Nijee Sharma BS Abstract Objectives/Hypothesis: To investigate the effects of various combinatorial treatments, consisting of a tapering dose of prednisone (P), a brief period of nerve electrical stimulation (ES), and systemic testosterone propionate (TP) on improving functional recovery following an intratemporal facial nerve crush injury. Study Design: Prospective, controlled animal study. Methods: After a right intratemporal facial nerve crush, adult male Sprague-Dawley rats were divided into the following eight treatment groups: 1) no treatment, 2) P only, 3) ES only, 4) ES + P, 5) TP only, 6) TP + P, 7) ES + TP, and 8) ES + TP + P. For each group n = 4,8. Recovery of the eyeblink reflex and vibrissae orientation and movement were assessed. Changes in peak amplitude and latency of evoked response, in response to facial nerve stimulation, was also recorded weekly. Results: Brief ES of the proximal nerve stump most effectively accelerated the initiation of functional recovery. Also, ES or TP treatments enhanced recovery of some functional parameters more than P treatment. When administered alone, none of the three treatments improved recovery of complete facial function. Only the combinatorial treatment of ES + TP, regardless of the presence of P, accelerated complete functional recovery and return of normal motor nerve conduction. Conclusions: Our findings suggest that a combinatorial treatment strategy of using brief ES and TP together promises to be an effective therapeutic intervention for promoting regeneration following facial nerve injury. Administration of P neither augments nor hinders recovery. Laryngoscope, 2010 [source] The effect of topical sodium thiosulfate in experimentally induced myringosclerosis,THE LARYNGOSCOPE, Issue 7 2010Yong Ho Park MD Abstract Objectives/Hypothesis: The purpose of this study was to investigate the effect of topical sodium thiosulfate (STS) in experimentally induced myringosclerosis (MS). Study Design: A prospective experimental animal study. Methods: Thirty Wistar albino rats were bilaterally myringotomized. The right ears were treated with STS or saline daily, and the left ears were left untreated and used as controls. The tympanic membranes were observed by otoendoscopy weekly, and tympanometric measurements were performed. All animals were histopathologically examined for myringosclerotic plaques. Results: Under otoendoscopy, myringosclerosis were observed around the handle of the malleus and near the annular region. The numbers of myringosclerotic ears were significantly more frequent in control and saline groups compared with the STS group (P < .05), and the formation of MS was more severe in control and saline groups compared with STS group (P < .05). Using tympanometric measurement, significantly reduced magnitudes of maximum admittance were observed in control and saline groups compared to normal and STS groups (P < .05). Under histopathologic examination, the tympanic membrane of the STS group appeared thinner than the control group (P < .05), with reduced calcium deposition than control and saline groups. Conclusions: Our results show that sodium thiosulfate has a preventive role in the development of myringosclerosis in the experimental animal model. Laryngoscope, 2010 [source] The effect of electrical and mechanical stimulation on the regenerating rodent facial nerve,THE LARYNGOSCOPE, Issue 6 2010Tessa Hadlock MD Abstract Objectives/Hypothesis: Investigators have long sought realistic methods to accelerate regeneration following nerve injury. Herein, we investigated the degree to which manual target muscle manipulation and brief electrical stimulation of the facial nerve, alone or in combination, affects recovery following rat facial nerve injury. Study Design: Prospective, randomized animal study. Methods: Sixty rats were randomized to three groups: brief electrical stimulation (BES), mechanical stimulation of the whisker pad (MEC), or both (COMBO). Animals underwent facial nerve transection and immediate microsurgical repair. In BES and COMBO groups, transection was preceded by 1-hour (3 V, 20 Hz square wave) electrical stimulation. Animals were tested weekly, with 5-minute recording sessions of whisker movement. In the MEC and COMBO groups, animals received 5 minutes of daily massage to the left whisker pad throughout the recovery period. Whisking behavior was analyzed for comparisons. Results: The BES and MEC groups demonstrated improved functional recovery in all whisking parameters compared with the COMBO group or historical controls at most time points between postoperative weeks 1 and 7. After 12 weeks, functional recovery remained superior in the BES and MEC groups compared with the COMBO and control groups, although the effect was no longer statistically significant. Conclusions: We observed an accelerative recovery effect of either electrical nerve stimulation or massage of the whisker pad on whisking behavior. The combination of both interventions had a negating effect on the acceleration of recovery. The potential clinical utility of these modalities bears consideration, and their negating interaction warrants further study. Laryngoscope, 2010 [source] Slow-release nanoparticle-encapsulated delivery system for laryngeal injection,THE LARYNGOSCOPE, Issue 5 2010Vasantha L. Kolachala PhD Abstract Objectives/Hypothesis: There is a need for a slow-release system for local delivery of therapeutics to the larynx. Most therapeutic substances, such as steroids or chemotherapeutic agents that are injected into the larynx are cleared rapidly. Repeated laryngeal injection of these substances at short intervals is impractical. Injectable encapsulated poly(lactide-co-glycolide) (PLGA) nanoparticles offer a potential slow-release delivery system for biologically active substances in the larynx. Study Design: Controlled animal study. Methods: PLGA nanoparticles were fabricated using a double emulsion method and were loaded with Texas Red-dextran (NPTR), hepatocyte growth factor (NPHGF), and bovine serum albumin (NPBSA). In vitro release of NPTR, NPBSA, and NPHGF was determined over approximately 2 weeks to assess potential duration of PLGA nanoparticle delivery. In vivo release of NPTR was assessed in a murine vocal fold injection model. The transcriptional effect of NPHGF on procollagen was measured in vitro to assess whether released growth factor retained functionality. Results: In vitro release kinetics demonstrated slow release of NPTR, NPBSA, and NPHGF over 12 to 14 days. In vitro NPTR release correlated with in vivo results. In vivo presence of NPTR occurred up to 7 days compared to 1 day for Texas Red control. In addition, NPHGF ameliorated transforming growth factor-, induced procollagen in vitro in 3T3 fibroblast cells. Conclusions: The results demonstrate the potential utility of nanoparticle encapsulation as an effective method for long-term delivery of specific drugs and biologically active substances to the larynx. Laryngoscope, 2010 [source] Comparison of extratemporal and intratemporal facial nerve injury models,THE LARYNGOSCOPE, Issue 12 2009Nijee Sharma BS Abstract Objectives/Hypothesis: The purpose of this study was to compare functional recovery and motor nerve conduction following a distal extratemporal crush injury of the facial nerve to a more proximal intratemporal crush injury. Study Design: Prospective, controlled animal study. Methods: Adult male Sprague-Dawley rats were divided into four experimental groups: 1) extratemporal crush, 2) extratemporal sham-operated, 3) intratemporal crush, and 4) intratemporal sham-operated. Each group had an n of 4,9. The facial nerve was crushed near its exit from the stylomastoid foramen for extratemporal facial nerve injuries and within the facial canal in the temporal bone for intratemporal facial nerve injuries. Recovery times for the return of facial nerve functional parameters were compared between the two injury models. Motor nerve conduction studies were also done weekly to quantify the changes in peak amplitude and latency of evoked response. Results: Rats receiving the extratemporal facial nerve injury recovered full facial function by ,2 weeks postoperative (wpo) and displayed normal peak amplitude and latency recordings by 4 wpo. In comparison, rats receiving the intratemporal facial nerve injury failed to reach complete functional recovery at the end of 8 wpo. Although latency of evoked response returned to normal by 2 weeks following the intratemporal injury, peak amplitude remained ,70% below normal at the end of 8 wpo. Conclusions: An intratemporal crush of the facial nerve leads to significantly delayed functional recovery and decreased motor nerve conduction as compared to an extratemporal crush, indicating that the location of injury strongly influences the recovery outcome. Laryngoscope, 2009 [source] Tissue-engineered trachea for airway reconstruction,THE LARYNGOSCOPE, Issue 11 2009Mark Weidenbecher MD Abstract Objectives/Hypothesis: Scaffold-free cartilage has been used to engineer biocompatible and mechanically stable neotracheas in vivo. The purpose of this animal study was to determine if neotracheal constructs, implanted paratracheally, could successfully be used for segmental tracheal reconstruction. Study Design: Animal study. Methods: Culture-expanded auricular rabbit chondrocytes were used to engineer scaffold-free cartilage sheets. Cartilage and a strap muscle flap were wrapped around a tube and implanted paratracheally. At 12 to 14 weeks postimplantation neotracheas were used to reconstruct 20 mm tracheal defects. Surgical technique was modified several times in an attempt to decrease the amount of neotracheal obstruction and fibrosis. In one of the six rabbits, neotrachea with its intact strap muscle flap was dropped into the defect followed by an end-to-end anastomosis; in two animals the muscle flap was partially, and in one rabbit completely removed. In two animals the muscle flap was partially removed, the tube reinserted, and the construct reimplanted for 5 weeks to allow formation of a fibrous lining over the exposed cartilage followed by tracheal reconstruction. Results: All implants developed into vascularized and mechanically sound neotracheas. Following reconstruction, none of the animals showed immediate signs of respiratory distress; however, one died after 24 hours due to extensive endotracheal muscle flap edema, whereas rabbits who had undergone partial or complete muscle flap removal survived up to 39 days before developing cicatricial stenosis. Conclusions: Tissue-engineered neotracheas proved to have excellent biocompatibility and stability to function under physiologic conditions, but lacked adequate endotracheal lining resulting in neotracheal stenosis. Laryngoscope, 2009 [source] Prostaglandin E2 is activated by airway injury and regulates fibroblast cytoskeletal dynamics,THE LARYNGOSCOPE, Issue 7 2009Vlad C. Sandulache MD Abstract Objectives/Hypothesis: To characterize the activation of cyclooxygenase (COX)-2/prostaglandin (PG) E2 signaling during airway mucosal repair and its subsequent role during the wound healing process. Study Design: Prospective animal study. Methods: The subglottis was approached via cricothyroidotomy. Sham airways were closed, and wounded airways were subjected to laser injury and closed. Subglottic tissue was harvested at 12 hours, 24 hours, 48 hours, and 72 hours postinjury. Secretions were collected preoperatively and at time of sacrifice. Inflammatory gene expression was analyzed using quantitative reverse transcriptase polymerase chain reaction. Subglottic/tracheal explants were exposed to exogenous IL-1, in the presence or absence of COX inhibitors. Explant-produced PGE2 levels were assayed using enzyme linked immunoassays. Human airway fibroblast migration and collagen contraction were assayed in the presence or absence of prostaglandin E2. Results: Laser injury triggers a rapid, dose-dependent increase in mucosal IL-1, and COX-2 gene expression, with an anatomical distribution proportional to the distance from the site of injury. Gene upregulation correlates with dose-dependent increases in PGE2 mucosal secretion levels. Ex vivo analysis indicates IL-1, is responsible for the activation of the COX-2 / PGE2 pathway. Prostaglandin E2 differentially inhibits airway fibroblast migration and contraction in a specific, dose-dependent manner. Conclusions: PGE2 is activated during mucosal inflammation and acts to decrease fibroplastic activity in the mucosal wound bed. During subglottic stenosis (SGS) development, the levels of PGE2 generated in response to injury may be insufficient to blunt the intrinsically fibroplastic phenotype of SGS fibroblasts, resulting in excessive scarring. Laryngoscope, 2009 [source] Changes of Extremity and Laryngeal Muscle Electromyographic Amplitudes After Intravenous Administration of Vecuronium,THE LARYNGOSCOPE, Issue 12 2008Yongbing Shi MD Abstract Objectives: To compare electromyographic (EMG) amplitude changes in extremity and laryngeal muscles after vecuronium administration and study the effects of topical lidocaine on laryngeal EMG in a swine model. Study Design: Prospective animal study. Methods: Electrically evoked EMG activities were recorded from the vocalis muscles (directly and via an EMG endotracheal tube) and from the flexor digitorum muscles before and after intravenous vecuronium administration. EMG amplitudes were followed for 30 minutes after vecuronium injection together with monitoring of limb twitches to train-of-four stimulation. The testing was repeated after a 30-minute wash-out period and with topical lidocaine. Results: EMG amplitude recovery occurred sooner and more quickly in flexor digitorum muscle than in vocalis muscles. Reappearance of four twitches corresponded to EMG amplitude recovery to about 80% of the baseline in flexor digitorum muscles and to about half-baseline size in vocalis muscles. EMG amplitudes were generally lower at the start of the second round testing than the first round, with somewhat slower recovery in vocalis muscles. Conclusions: In contrast to reports by others in human studies, extremity muscles seem to be more resistant to vecuronium at 0.1 mg/kg than laryngeal muscles in the swine. Reappearance of four twitches corresponds to 50% of laryngeal EMG recovery and indicates adequate condition for monitoring electrically evoked laryngeal EMG activities. This study is inconclusive regarding the effects of topically applied lidocaine on laryngeal EMG amplitudes. Translation of these data to humans should be done with caution. [source] Comparison of Animal Models for Head and Neck Cancer Cachexia,THE LARYNGOSCOPE, Issue 12 2007Trinitia Cannon MD Abstract Objectives/Hypothesis: Despite its negative impact on cancer patients, there are few animal models of cancer cachexia. Our hypothesis was that different human cell lines would variably induce cachexia. Study Design: Prospective animal study. Methods: We established two xenograft models in athymic mice and compared these with a cachexigenic cell line, the murine adenocarcinoma 16 (MAC16) cell line. Eight-week-old female, athymic mice were injected with human head and neck cell lines (JHU022, JHU012) and the MAC16 cell line. Body weight, food intake, body composition, leg weights, serum cytokines, and lipid mobilizing factor (LMF) were compared. Results: Mean food intake for all groups was equivalent. Mean percent change in body weight after 18 days was 18%, 19%, 12%, and 3% for control, JHU012, JHU022, and MAC16 experimental groups, respectively. Both JHU022- and MAC16-injected mice showed wasting even when tumor burden was low. In contrast, mice injected with JHU012 developed larger tumors yet lacked evidence of cachexia. These mice demonstrated loss of lean body mass but not fat mass. Serum cytokine levels for interleukin (IL)-1, and IL-1, were elevated in JHU022-bearing mice, whereas IL-1,, IL-6, interferon (IFN)-,, and tumor necrosis factor alpha (TNF)-, were elevated in MAC16-bearing mice. LMF was present in both the JHU022 and JHU012 cell lines. Conclusions: The JHU022 cell line caused more severe cachexia than the JHU012 cells, suggesting these cell lines may be used to further study cancer cachexia. IL-1, and IL-1, in the JHU022 model may be mediators of cachexia, whereas TNF-,, IFN-,, and IL-6 may be mediators in MAC16-induced cachexia. [source] A Potential Portal Flow in the Inner Ear,THE LARYNGOSCOPE, Issue 2 2007Morten Friis MD Abstract Objectives/Hypothesis: The aim of the present study was to visualize the flow direction of blood in the extraosseous part of the vein of the vestibular aqueduct (VVA) and to explore the effect of an induced obstruction in the distal part of the VVA before it merges with the sigmoid sinus. The endolymphatic sac has been implicated as a potential endocrine gland, which venules drain to the VVA. A reversal of the direction of flow in the VVA toward the inner ear could, through vestibular arteriovenous anastomosis, cause portal circulation in the inner ear. Study Design: The authors conducted an experimental animal study using in vivo fluorescence microscopy. Results: Obstructing the distal part of the VVA just before it empties into the sigmoid sinus immediately reverses the flow of blood in the VVA toward the inner ear. Conclusions: After an obstruction of the VVA, the drained venous blood from the endolymphatic sac may enter a portal circulation in the inner ear, which could cause disturbances in the endolymph homeostasis and potentially symptoms as seen in Meniere disease. [source] Chemopreventive Effect of Celecoxib in Oral Precancers and Cancers,THE LARYNGOSCOPE, Issue 10 2006Lining Feng PhD Abstract Objectives: Oral cancer has become an important health care problem in many countries. Because this disease develops slowly, early detection and intervention can greatly affect ultimate outcome. Celecoxib is a cyclooxygenase-2 inhibitor with significantly less toxicity. This study investigated the possibility of using it for chemoprevention of oral cancer at the early stages. Study Design: Randomized animal study. Methods: Dysplastic lesions were induced in the buccal pouches of 47 hamsters by a 5 week painting of 9,10-dimethl-1,2-benzanthrancene (DMBA). Basal diets or diets containing 500 or 1,500 ppm of Celecoxib were orally given for 7 weeks. The T50 (50% incidence; i.e., the time to appearance of tumors in 50% of the hamsters) was observed, and volume of tumors was measured on day 1, 9, 19, 28, 35, and 48 with the Celecoxib treatment. Results: The T50 was 9, 19, and 28 days with the treatment in the control group, in the 500 ppm group, and in the 1,500 ppm group, respectively. It indicated that the Celecoxib treatment could delay progression of early lesion. The tumor measurement showed that this treatment was also effective in delaying tumor growth in both treatment groups. There was a difference in the treatment efficacy between the 500 ppm and 1,500 ppm of Celecoxib, indicating a dose-dependent efficacy. Conclusions: Celecoxib is effective in delaying onset of early lesions induced by DMBA and in slowing growth of the tumors in hamster cheek pouches during the postinitiation stage. Its treatment efficacy appears to be dose dependent. [source] Cochlear Preservation After Meningitis: An Animal Model Confirmation of Adjunctive Steroid Therapy,THE LARYNGOSCOPE, Issue 2 2006John Addison MA Abstract Objective/Hypothesis: The objective of the present study was to determine whether treating pneumococcal meningitis with a combined antibiotic and steroid regime will prevent cochlear damage, a common pneumococcal meningitis side effect. Study Design: This was a prospective animal study. Methods: Gerbils were randomly assigned to three experimental groups. Animals in group 1, the control animals, received intrathecal saline injections. Animals in groups 2 and 3 received intrathecal injections of Streptococcus pneumoniae to induce meningitis. Although group 2 solely was treated for 7 days with intraperitoneal penicillin injections (48,0000 units), group 3 received, in addition to the antibiotic for 4 days, 0.5 mg/kg intraperitoneal dexamethasone injections. Three months after the meningitis was induced, the animals' cochlear function was determined using auditory brainstem responses (ABRs). Fifteen frequencies were tested, five octaves at three steps per octave between 2 and 50 kHz. Results: ABR thresholds were significantly elevated only in group 2. When compared with group 1, ABR thresholds were 19 dB higher (P < .05). Frequencies at the low-frequency end of the hearing range were affected more than the midfrequencies. Animals that received dexamethasone had 2-dB higher thresholds than the control group (P > .05). Conclusions: Dexamethasone therapy in conjunction with antibiotic therapy preserves cochlear function in cases of S. pneumoniae meningitis in the Mongolian gerbil model. [source] Time and Dose Effects of Mitomycin C on Extracellular Matrix Fibroblasts and Proteins,THE LARYNGOSCOPE, Issue 1 2005Bryce Ferguson Abstract Objectives/Hypothesis: The objective was to determine treatment dose and time-dependent effects of injected mitomycin C on extracellular matrix fibroblasts, collagen, and fibronectin, important mediators in the wound healing response, in a rat cutaneous wound model. Study Design: A prospective, controlled animal study. Methods: Forty rats were injected with three different doses (0.4, 2.3, and 5.0 mg/mL) of mitomycin C at three different wound sites with a fourth wound site receiving saline as a control. The rats were grouped to have their tissue harvested at five different dates ranging from 1 week to 8 weeks. After death, samples from the wound site underwent Western blot analysis for collagen and fibronectin and histological analysis measuring fibroblast apoptosis. Results: Over an 8-week period, collagen and fibronectin significantly decreased and fibroblast apoptosis significantly increased. No correlation was found between the injected dose of mitomycin C and either the extracellular matrix protein concentration or the rate of fibroblast apoptosis. Conclusion: Mitomycin C demonstrated a long-term effect in a wound, inhibiting collagen and fibronectin production and inducing apoptosis. Use of mitomycin C in excess of 0.4 mg/mL did not alter protein concentrations or rate of apoptosis. [source] Determination of Reactive Oxygen Species in Myringotomized Tympanic Membranes: Effect of Vitamin E TreatmentTHE LARYNGOSCOPE, Issue 4 2004Senol Polat MD Abstract Objectives/Hypothesis Recent studies have established a strong relationship between the development of myringosclerosis and reactive oxygen species (ROS). The aims of the present study were to directly detect ROS in the tympanic membrane and middle ear mucosa of rats by measuring luminol amplified chemiluminescence, to evaluate the changes in the levels of ROS after treatment with vitamin E, and to examine the possible changes in the tympanic membranes otomicroscopically and histologically. Study Design Prospective controlled animal study. Methods Forty healthy Sprague-Dawley rats were divided into five groups of eight animals each. Animals in all groups except group 1 were bilaterally myringotomized. Group 2 received no treatment, group 3 was treated with topical olive oil, group 4 received topical vitamin E, and group 5 received intramuscular vitamin E. After 24 hours of myringotomy, tympanic membranes were examined otomicroscopically; thereafter, tympanic membranes and middle ear mucosa were peeled off. The right ears of the animals were used for biochemical assay, and the left ears were used for histological study. Results Reactive oxygen species levels were significantly decreased in group 4 with topical application of vitamin E compared with untreated and myringotomized animals in group 2. Reactive oxygen species levels were also decreased in group 5, although the decrease was not statistically significant when compared with groups 2 and 3. Histological studies confirmed sclerotic changes in the untreated myringotomized animals. The tympanic membranes of animals in groups 2 and 3 showed a white, chalk-like pattern of sclerotic changes, whereas animals in groups 4 and 5, with the exception of two animals in group 5, lacked these changes. Conclusion Although the relationship between the development of myringosclerosis and ROS had been well documented previously, the present study is the first that has directly measured the levels of ROS in the tympanic membrane and middle ear mucosa. These results are relevant because they correlate with histological findings. It has also been demonstrated that topically applied vitamin E is effective in decreasing the ROS levels. [source] Antiangiogenic and Chemopreventive Activities of Celecoxib in Oral Carcinoma Cell,,THE LARYNGOSCOPE, Issue 5 2002Zhi Wang MD Abstract Objectives Chemoprevention is a promising strategy to inhibit carcinoma before invasive tumors develop, but a new molecular target is desirable. Celecoxib is a newly developed cyclo-oxygenase (COX)-2 inhibitor with significantly less toxicity. The study was conducted to determine whether celecoxib is effective and safe in prevention of oral cancer. The antiangiogenic activity of celecoxib was studied to explore the potential mechanism involved. Study Design Randomized animal study. Methods The study consisted of two phases. In the phase 1, 10 mice were used to determine the efficacy and safety of celecoxib with intradermal inoculation with oral carcinoma cells. The 10 mice were equally divided into two groups 5 mice (30 inoculated sites) in each group to receive 1,500 parts per million (ppm) celecoxib mixed in with the diet or to eat a normal diet, respectively, for 21 days. In phase 2, 10 more mice were inoculated to determine the effect of celecoxib on angiogenesis. Five mice received 3,000 ppm celecoxib in the diet, with the other five mice as control animals. The antiangiogenic activity was evaluated by comparing the density of newly growing microvessels after the inoculation. Results The results indicated that celecoxib significantly delayed cell growth and reduced tumor volume. There was statistical significance in the quantity of new vasculature in the tumor sites between the two groups. No toxic effect was found by means of measurement of body weight loss and microscopic dissection of organs. Conclusions The study provided the first evidence to show the chemopreventive efficacy of celecoxib on oral cancer in a nude mouse model. Clinical trials are warranted to determine the efficacy in humans. [source] Lateralization During the Weber Test: Animal ExperimentsTHE LARYNGOSCOPE, Issue 3 2002Jean-Yves Sichel MD Abstract Objectives/Hypothesis The objective of this study were to present an assessment of a new theory to explain lateralization during the Weber test using an animal model. This theory is based on the discovery that a major pathway in bone conduction stimulation to the inner ear is through the skull contents (probably the cerebrospinal fluid [CSF]). The placement of a bone vibrator or tuning fork on the skull excites the inner ear by the classic osseous pathway and by the suggested CSF pathway. We assume that there is a phase difference between the stimulation mediated by the ossicular chain (inertial and occlusion mechanisms) and the one mediated by the CSF. The presence of a conductive pathology will decrease the magnitude of the sound energy mediated by the ossicular chain. Thus, the out-of-phase signal arriving through the bony pathways will be decreased, hence increasing the resultant sound intensity stimulating the cochlea. Study Design Prospective animal study. Methods The experiment was performed on 10 fat sand rats, which had undergone unilateral cochleostomy and a small craniotomy. The auditory nerve brainstem response (ABR) thresholds were measured to air-conducted stimulation, to stimulation with the bone vibrator applied to the skull, and to stimulation with the bone vibrator applied directly to the brain through the craniotomy. The ossicular chain of the second ear was then fixed to the middle ear walls with cyanoacrylate glue to induce a conductive hearing loss. The ABR thresholds to the same three stimuli were then measured again. Results After ossicular chain fixation, the ABR threshold to air-conducted stimulation increased, to bone vibrator stimulation on the bone decreased (hearing improvement), and to bone vibrator stimulation directly on the brain remained unchanged. Conclusions This experiment confirms the proposed theory. During clinical bone conduction stimulation, there is a phase difference between sound energy reaching the inner ear through the middle ear ossicles and from the CSF. A middle ear conductive pathology removes one of these components, thus increasing the effective sound intensity in the affected ear. On the other hand, when the bone vibrator is applied on the brain, the inner ear is stimulated only through the CSF, so ossicular chain fixation does not change the ABR threshold. Moreover, this study proves that lateralization during the Weber phenomenon is the result, at least in part, of an intensity difference between sound energy reaching the two cochleae. [source] Fascia Augmentation of the Vocal Fold: Graft Yield in the Canine and Preliminary Clinical Experience,THE LARYNGOSCOPE, Issue 5 2001Sanford G. Duke MD Abstract Introduction Glottal insufficiency resulting from vocal fold bowing, hypomobility, or scar is frequently treated by injection augmentation. Injection augmentation with fat, collagen, gel foam, polytef, and recently, fascia lata has been previously reported. Variable graft yield and poor host-tissue tolerance have motivated the continued search for an ideal graft substance. Study Design A prospective trial of autologous fascia augmentation of the vocal cord in the human and in an animal model. Methods Autologous fascia injection augmentation (AFIA) was evaluated in 8 canines and 40 patients at our institution between 1998 and 2000. The animal study compared graft yield from AFIA with autologous fat yield. The outcome measure was graft yield calculated from histological examination of larynges 12 weeks after injection augmentation. Clinical trial outcome measures included symptom surveys, acoustical voice analyses, and subjective voice assessments. Mean follow-up was 9 months. Results In the canine larynx, the mean graft yield for AFIA was 33% (range, 5%,84%) compared with autologous lipoinjection (47%; range, 7%,96%;P = .57). Subjective improvement in vocal quality was reported by 95% of patients (38 of 40) after AFIA. Preoperative and postoperative voice analysis data were obtained from 26 patients. Subjective voice rating demonstrated a significant improvement after AFIA (P <.0001). Acoustical parameters of jitter, shimmer, noise-to-harmonic ratio, phonatory range, and degree unvoiced improved significantly (P <.05) in all patients after fascia augmentation. Conclusions Based on the animal study, we concluded that graft yields are excellent but variable for AFIA. The result is similar in variability and overall yield to autologous lipoinjection. Subjective and objective analyses of voice outcomes after AFIA are universally improved. Fascia appears to be an excellent alternative to lipoinjection in properly selected cases of glottic insufficiency. [source] | ||||||||||