Low dose pramipexole causes D3 receptor-independent reduction of locomotion and responding for a conditioned reinforcer.

Pramipexole is a clinically important dopamine receptor agonist with reported selectivity for dopamine D3 receptors over other dopaminergic and non-dopaminergic sites. Many of its behavioural effects are therefore attributed to D3 receptor activity. Here we relate pramipexole's ex vivo D2 and D3 receptor binding (measured using [(3)H]-(+)-PHNO binding experiments) to its effects on locomotion and operant responding for primary and conditioned reinforcers. We show that pramipexole has inhibitory behavioural effects on all three behaviours at doses that occupy D3 but not D2 receptor. However, these effects are 1) not inhibited by a D3 selective dose of the antagonist SB-277011-A, and 2) present in D3 receptor knockout mice. These results suggest that a pharmacological mechanism other than D3 receptor activity must be responsible for these behavioural effects. Finally, our receptor binding results also suggest that these behavioural effects are independent of D2 receptor activity. However, firmer conclusions regarding D2 involvement would be aided by further pharmacological or receptor knock-out experiments. The implications of our findings for the understanding of pramipexole's behavioural and clinical effects are discussed.

Retrospective analysis of the impact of HPV status and smoking on mucositis in patients with oropharyngeal squamous cell carcinoma treated with concurrent chemotherapy and radiotherapy.

OBJECTIVES: The standard concurrent radiotherapy and chemotherapy regimens for patients with oropharyngeal cancer are highly toxic. Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has recently emerged as a distinct biological and clinical entity with improved response to treatment and prognosis. A tailored therapeutic approach is needed to optimize patient care. The aim of our study was to investigate the impact of HPV and smoking status on early toxicities (primarily mucositis) associated with concurrent chemotherapy and radiotherapy in patients with OPSCC. MATERIALS AND METHODS: We retrospectively evaluated 72 consecutive patients with OPSCC and known HPV status treated with concurrent radiotherapy and chemotherapy at our institution. Treatment-related toxicities were stratified by smoking and HPV status and compared using univariate and multivariate logistic regression. RESULTS: HPV-positive patients had a 6.86-fold increase in the risk of having severe, grade 3-4 mucositis. This effect was preserved after adjusting for patient smoking status, nodal stage, radiotherapy technique and radiotherapy maximum dose. Additionally, HPV status had significant effect on the objective weight loss during treatment and at three months after treatment. Consistently, non-smokers had a significant 2.70-fold increase in the risk of developing severe mucositis. CONCLUSION: Risk factors for OPSCC modify the incidence of treatment-related early toxicities, with HPV-positive and non-smoking status correlating with increased risk of high grade mucositis and associated outcomes. Retrospective single-institution studies need to be interpreted cautiously. However, this finding is important to consider when designing therapeutic strategies for HPV-positive patients and merits further investigation in prospective clinical trials.

Responding for conditioned reinforcement in C57BL/6 and CD-1 mice, and Sprague-Dawley rats: Effects of methylphenidate and amphetamine.

RATIONALE: Characterization of responding for conditioned reinforcement in mice is important to implement genetic tools in examining the neurobiological mechanisms underlying reward-related learning and incentive motivation. METHODS: Inbred C57BL/6 mice, outbred CD-1 mice, and outbred Sprague-Dawley rats underwent Pavlovian conditioning in which a conditioned stimulus (CS) was paired with saccharin. Subsequently, subjects were allowed to respond for that CS in tests of responding for conditioned reinforcement. Experiments measured the effects of methylphenidate (MPH) and amphetamine (AMPH) on lever pressing for conditioned reinforcement in mice and rats. We further examined the stability of responding for conditioned reinforcement in mice after repeated testing and the extinction of this behaviour following omission of the reinforcer. We also determined whether the CS exhibited reinforcing properties if it was not paired with saccharin. RESULTS: C57BL/6 and CD-1 mice learned to respond for a conditioned reinforcer similarly to rats, and the behaviour was stable over time. MPH increased responding in CD-1 mice and rats, but not in C57BL/6 mice. AMPH only increased responding in rats. Responding was reduced following omission of the conditioned reinforcer, and responding was only established when the CS was paired with saccharin. CONCLUSIONS: These experiments characterize a conditioned reinforcement test which produces stable responding in two different mouse backgrounds. These findings also show that dopaminergic psychomotor stimulants can differently affect rats and mice in tests of responding for conditioned reinforcement.

Distribution of c-Fos immunoreactivity in the rat brain following abuse-like toluene vapor inhalation.

Inhalation of vapors from toluene-containing products results in euphoria accompanied by a variety of cognitive impairments and motor dysfunctions. The profound behavioral changes observed during and following toluene inhalation suggest changes in the activity of cells in potentially many brain regions; however, a comprehensive assessment of the neuroanatomical structures activated by toluene vapor has not been completed. Thus in the present study we systematically mapped in over 140 brain structures the distribution of c-Fos immunoreactivity (c-Fos IR), a proxy for neural activation, following exposure to an abuse-like concentration (~5000 ppm) of toluene vapor for 0, 5, 10 or 30 min. Quantitative analyses revealed increases in c-Fos IR in about one-third of the brain structures examined, with most of these structures significantly activated only after prolonged toluene exposure. The majority of brain structures activated by toluene were found in the forebrain and midbrain, with particularly pronounced activation in nuclei implicated in the processing of rewarding, emotional, and olfactory stimuli, and those controlling motor output. These structures included the ventral tegmental area, nucleus accumbens, select regions of the amygdala and hypothalamus, cingulate cortex, olfactory nuclei, piriform cortex, secondary motor cortex and caudate-putamen. In contrast, all subregions of the hippocampus and most thalamic nuclei were not significantly activated by toluene vapor. In the brainstem, effects of toluene vapor were restricted to select nuclei in the pons. The pattern of c-Fos IR evoked by inhalation of toluene vapor appears distinct from other psychoactive substances, consistent with the unique and complex behavioral outcomes associated with acute toluene inhalation.

The midfacial degloving procedure for nasal, sinus, and nasopharyngeal tumors.

The midfacial degloving approach is more technically involved than a lateral rhinotomy and requires a basic level of proficiency and understanding of closed rhinoplasty incisions and anatomy of the nose, paranasal sinuses, and skull base structures. Current applications of the midfacial degloving procedure have allowed expansion of indications for this technique through the use of complementary endoscopic and subcranial approaches, permitting the exposure and removal of extensive skull base lesions without disfiguring facial incisions. Fundamental in these approaches is the basic midfacial degloving exposure, which is discussed in this article, along with the applications for treatment of skull base lesions.

Endovascular treatment of hemorrhage after tonsillectomy in children.

SUMMARY: Endovascular therapy for hemorrhage after tonsillectomy or adenoidectomy is an important adjunct to the definitive treatment of this life-threatening occurrence. We report two cases of hemorrhage after tonsillectomy and/or adenoidectomy and describe the endovascular management of this complication in children.

Temporal approach for resection of juvenile nasopharyngeal angiofibromas.

OBJECTIVE: To describe a lateral preauricular temporal approach for resection of juvenile nasopharyngeal angiofibroma (JNA). STUDY DESIGN: A retrospective review of five patients with JNA tumors that were resected by a lateral preauricular temporal approach. METHODS: The medical records of five patients who underwent resection of JNA tumors via a lateral preauricular temporal approach were reviewed, and the following data collected: tumor extent, blood loss, hospital stay, and surgical complications. RESULTS: Five patients with JNA tumors had resection by a lateral preauricular temporal approach. These tumors ranged from relatively limited disease to more extensive intracranial, extradural tumors. Using the staging system advocated by Andrews et al., these tumors included stages II, IIIa, and IIIb. Four patients (stages II, IIIa, IIIa, and IIIb) who underwent primary surgical excision had minimal blood losses and were discharged on the first or third postoperative day with minimal transient complications (mild trismus, frontal branch paresis, serous effusion, and cheek hypesthesia). The remaining patient (stage IIIb) did well after surgery, despite having undergone preoperative radiation therapy and sustaining a significant intraoperative blood loss. There have been no permanent complications or tumor recurrences. CONCLUSIONS: A lateral preauricular temporal approach to the nasopharynx and infratemporal fossa provides effective exposure for resection of extradural JNA tumors. The advantages of this approach include a straightforward route to the site of origin, the absence of facial and palatal incisions, and avoidance of a permanent ipsilateral conductive hearing loss.

Preservation of olfaction in anterior skull base surgery.

OBJECTIVES/HYPOTHESIS: In selected unilateral tumors and defects of the anterior skull base, the preservation of contralateral olfaction is achievable through a localized subcranial approach without compromising surgical objectives of resection or repair. STUDY DESIGN: Description of a functional adaptation of anterior skull base surgical techniques through a retrospective patient series. METHODS: Nine patients underwent anterior skull base surgery for unilateral cribriform plate disease including four malignant and two benign tumors, two encephaloceles, and one iatrogenic cribriform injury with cerebrospinal rhinorrhea. All nine patients consented to a localized subcranial approach to the anterior skull base to preserve the contralateral olfactory nerves. In four patients with benign disease a portion of the ipsilateral nerves was additionally conserved. Postoperative olfaction was assessed objectively with a commercially available smell test. Indications, technique, results, and complications are reported and discussed. RESULTS: All patients had eradication of disease with preservation of functional olfaction CONCLUSIONS: Conservation of olfaction is possible in selected cases of anterior skull base surgery when the lesion is unilaterally confined.

Evaluation of airway obstruction using virtual endoscopy.

OBJECTIVES: This study examines the use of virtual endoscopy (VE) in the evaluation of patients with upper airway obstruction. The utility of VE compared with actual endoscopy was investigated with respect to accuracy of diagnosis and reproduction of endoscopic images. STUDY DESIGN: A random cohort of 30 patients with various causes of airway obstruction was examined. METHODS: The computed tomography (CT) data were reconstructed using a proprietary VE software program, FreeFlight, blind to the actual endoscopic findings. The cause of obstruction was identified and compared with actual endoscopic findings. This included 21 patients with airway stenoses, 8 patients with laryngotracheomalacia, 3 tracheal tumors, 2 glottic webs, 5 patients with innominate artery compression, 2 tracheal granulomas, and 7 patients with impaired true vocal cord mobility. RESULTS: Virtual endoscopic evaluation was accurate in assessing stenosis width and length of fixed airway lesions. Correlation of stenosis shape and contour between actual endoscopy and VE was excellent. The stenosis-to-lumen ratios were compared between VE and actual endoscopy and were found to be within 10% (SD = 8). However, virtual endoscopic evaluation could not illustrate one of the glottic webs, half of the cases of tracheomalacia, or any of the cases of impaired true vocal cord mobility. CONCLUSIONS: Virtual endoscopy was not as sensitive as actual endoscopy in detecting the cause of airway obstruction that was based on dynamic movement. However, VE was excellent for the measurement and definition of fixed airway lesions.

Benefits of routine maxillectomy and orbital reconstruction with the rectus abdominis free flap.

Maxillary defects lead to functional and cosmetic deficiencies, especially with tumor invasion of the orbit and cribriform plate. Additionally problematic is the near-total palatal resection in patients with poor dentition (ie, not useful for anchoring obturators) and the desire for return of deglutition and useful speech. A series of 12 patients is presented in whom a rectus abdominis free flap was used for reconstruction of the palate, maxilla, and/or orbit. Nine of 12 free flaps were used to reconstruct defects involving the maxilla and orbit; all were successful in restoring hard palate continuity and function without the use of an obturator. The remaining 3 patients underwent successful repair of defects involving the orbit and medial maxilla without complication. Four of those 9 patients with palatal reconstruction augmented their dental rehabilitation with either their existing upper denture plate or the use of a cosmetic appliance anchored to their remaining dentition. Objectively, the rectus abdominis myocutaneous free flap proved to be a reliable and expeditious method of restoring function and acceptable cosmesis. We believe this technique should be routinely considered in the reconstruction of these defects.

The effect of endothelial cell growth factor on peripheral nerve regeneration.

Neural regeneration after grafting can be unpredictable. In an effort to enhance the return of function after cable grafting, we studied the effects of an angiogenic factor, endothelial cell growth factor (ECGF), on regenerating nerves. Cable grafts on the sciatic nerve were established in 18 rats and treated with ECGF or a control saline solution. At 5 weeks, nerve conduction studies were performed, and the animals were killed for histologic measurements of graft vascularity and axon counts. A significant increase in vascularity was noted in the treated group versus the control group; neither the axon counts nor the nerve conduction velocities differed significantly between the two groups, although the treated group appeared to show improved neural conduction compared with the control group.

Management of nonepidermoid cancer of the larynx.

Nonepidermoid cancer of the larynx represents an extremely diverse group of diseases with differing prognoses and rationales of management. With the lack of specificity in symptoms and physical findings, proper and expeditious lesion characterization is therefore dependent on a high index of suspicion by the clinician and accurate consulting histopathology. These neoplasms can be grouped according to cells with secretory, connective tissue, lymphoreticular, or metastatic origins. Based upon this framework, this article discusses the unique aspects of these various diseases that can lead to their diagnosis, along with consideration of management options and prognostic variables.

Desmoplastic malignant melanoma of the oral mucosa. An underrecognized diagnostic pitfall.

BACKGROUND: Although cutaneous desmoplastic malignant melanoma (DMM) has been well characterized, those arising from the oral mucosa have been less well defined. METHODS: We evaluated the clinical and pathologic features of three patients with biopsy-proven DMM examined at the North Carolina Baptist Hospital. Routine hematoxylin and eosin-stained slides were reviewed in all three cases. Sections from all cases were examined immunohistochemically using the avidin-biotin-peroxidase (ABC) technique and employing commercially available antibodies to the following antigens: S-100 protein, HMB-45, NK1C3, and cytokeratin (AE1/AE3). Appropriate positive and negative controls were utilized throughout these procedures. Clinical data were obtained from the patients' medical records. RESULTS: Age at diagnosis for the three male patients were 42, 64, and 75 years. Anatomically, these neoplasms arose from the left maxillary oral mucosa (two patients) and the vermilion border of the lower lip (one patient). Initial incisional biopsies of all three patients were misinterpreted as desmoid tumor (one patient) and squamous cell carcinoma (two patients), respectively. Histologically, all tumors were poorly circumscribed and composed of fascicles and bundles of spindle-shaped cells with hyperchromatic nuclei and associated with extensive stromal collagenization. Perineural invasion was noted in two tumors. An overlying atypical, intraepidermal melanocytic proliferation was observed in two tumors. Immunohistochemically, all three tumors showed positive immunoreactivity with S-100 protein and vimentin. One tumor also expressed HMB-45. Wide surgical incision was the primary mode of therapy in all patients. One patient also received multiple courses of radiation therapy and chemotherapy. One patient died of widespread metastatic disease. CONCLUSIONS: DMM of the oral mucosa is a rare, often unrecognized, form of malignant melanoma associated with a fibrosarcoma-like morphologic appearance and abundant collagenization. Meticulous attention to histomorphology and judicious use of immunohistochemical stains will help prevent misdiagnosis.

Effect of intermittent acid and pepsin exposure on burned esophageal mucosa.

PURPOSE: To determine if gastroesophageal reflux affects the healing of esophageal mucosa damaged by alkaline substances. MATERIALS AND METHODS: In a rabbit model, the effects of intermittent acid and pepsin exposure (thereby mimicking gastroesophageal reflux) on post-caustic-burn esophageal mucosa were examined. Exposures were group I (n = 9), sodium hydroxide exposure alone; group II (n = 9), daily acid and pepsin exposure; and group III (n = 8), sodium hydroxide, then daily acid and pepsin exposure. After 3 weeks, the animals were killed and their esophagi examined. RESULTS: Grossly, specimens in group II appeared normal; specimens in groups I and III were abnormal, displaying some scar tissue, but were not significantly different. Histologically, the differences between groups I and III approached significance. Increased numbers of intraepithelial eosinophils were seen in those specimens exposed to reflux. CONCLUSIONS: Gastroesophageal reflux may retard the healing of injured esophageal mucosa and should be studied further in an effort to improve the care of patients who sustain alkaline esophageal burns.

Spontaneous cerebrospinal fluid otorrhea from defects of the temporal bone: a rare entity?

Cerebrospinal fluid (CSF) otorrhea is usually associated with a history of trauma or previous surgery. Spontaneous CSF otorrhea is uncommon. When such spontaneous CSF leakage occurs, it may be associated with dural herniation, with the production of conductive hearing loss from impingement on the ossicles. This type of leakage has characteristic findings which, if recognized, can lead to earlier diagnosis and avoidance of complications. A review of the world literature revealed 44 reported cases. This report presents the authors' experience with 12 patients with spontaneous CSF leakage from temporal bone defects. This entity may be more prevalent than is reported. The differential diagnosis and management of CSF otorrhea (secondary to temporal bone defects) are discussed and representative cases are presented.

Gunshot wounds to the mandible and midface: evaluation, treatment, and avoidance of complications.

As American society becomes progressively violent, an ever-increasing number of gunshot wounds are being seen across the United States. Particularly challenging are injuries that involve the mandible and midface, not only because of problems with reconstructing bone and soft-tissue defects but also because of emergent problems with airway obstruction and neurovascular compromise. We present 40 cases of gunshot wounds to the mouth, mandible, and maxilla treated at Wake Forest University Medical Center during the past 7 years. The focus of this retrospective analysis is on emergency evaluation and treatment, complications encountered, and operative techniques used for reconstruction. Special emphasis is placed on recognizing and avoiding the complications of these injuries.

Lateral orbital/anterior midfacial degloving approach for nasopharyngeal angiofibromas with cavernous sinus extension.

A case of nasopharyngeal angiofibroma removed through a modified lateral approach for an infratemporal fossa resection is reported. This modification involved removing the bone of the lateral orbital apex and posterior middle fossa to expose the dura and periorbita and, when combined with a midfacial degloving approach, provided full access to the tumor abutting the cavernous sinus extradurally while preserving middle ear function.

Surgical therapy of glomus vagale tumors.

Lying between the carotid bifurcation and the jugular foramen, glomus vagale tumors share characteristics with paragangliomas of those two structures, such as invasion of the carotid artery, destruction of the skull base, and cranial neuropathies. This capability for local invasion provides a therapeutic challenge with regard to the proper assessment of tumor extent and the selection of appropriate treatment. In order to clarify an approach to the management of glomus vagale tumors, we reviewed a 10-year experience with 15 patients treated for this tumor at the University of Zürich Department of Otolaryngology, using a new system of classification. This system highlights the relative position of a vagal paraganglioma to the jugular foramen and is helpful in designing the proper therapy. Pitfalis in surgical technique, recommended preoperative evaluation, and the roles of balloon occlusion and irradiation in the treatment of these tumors, are discussed.

Transotic approach to the cerebellopontine angle.

The transotic approach to the cerebellopontine angle for resection of tumors invading the internal auditory canal provides superior illumination and exposure for optimal preservation of facial nerve function. Separation of facial nerve from tumor is enhanced with an anterior exposure that allows visualization of the intracranial segment of the nerve before tumor removal without significantly increasing total operative time. Facial nerve grafting or hypoglossal-facial anastomosis may be incorporated into the procedure at the time of tumor resection using the transotic approach. When combined with a musculofascial patch secured to the dural defect, the initial subtotal petrosectomy with eustachian tube and middle ear cleft obliteration generally avoids the complication of an immediate or delayed postoperative cerebrospinal fluid leak. The transotic approach is indicated for tumors up to 2.5 cm in size that are not adherent to the brain stem.