Sequence-dependent cytotoxic effects due to combinations of cisplatin and the antimicrotubule agents taxol and vincristine.

The antineoplastic activity that taxol has demonstrated in advanced ovarian cancer and other neoplasms in which the platinum analogues are among the most active agents has been the impetus for the development of taxol/platinum combination regimens. Since both classes of agents are known to induce cell-cycle-dependent effects and to delay cell-cycle traverse in specific phases of the cycle, an evaluation of drug sequence dependence was incorporated into initial clinical studies of the drug combination. To complement clinical studies, sequence-dependent interactions were assessed in vitro using L1210 leukemia. Cytotoxicity resulting from the combination of taxol and cisplatin was significantly increased over that achieved with cisplatin alone only when cisplatin was administered after taxol. This sequence was significantly superior to both the reverse sequence and to simultaneous drug treatment. Results achieved with sequence iterations of vincristine and cisplatin were nearly identical. In addition, alkaline-elution studies, using the optimal sequence of cisplatin and either taxol or vincristine, demonstrated that these antimicrotubule agents do not increase the formation of cisplatin-induced DNA interstrand and DNA-protein crosslinking over that produced by cisplatin alone. Although the mechanisms for the sequence-dependent cytotoxic interactions between cisplatin and the antimicrotubule agents have not been determined, it is likely that antagonistic interactions occur with the suboptimal sequences, probably because of cell-cycle-dependent phenomena.

Ergothioneine, histidine, and two naturally occurring histidine dipeptides as radioprotectors against gamma-irradiation inactivation of bacteriophages T4 and P22.

Bacteriophages P22, T4+, and T4os (osmotic shock-resistant mutant with altered capsids) were diluted in 0.85% NaCl and exposed to gamma irradiation (2.79 Gy/min) at room temperature (24 degrees C). T4+ was more sensitive to inactivation than was P22, and the T4os mutant was even more sensitive than T4+. Catalase exhibited a strong protective effect and superoxide dismutase a weaker protection, indicating that H2O2 or some product derived therefrom was predominant in causing inactivation of plaque formation. Low but significant (0.1-0.3 mM) reduced glutathione (GSH) enhanced phage inactivation, but a higher (1 mM) GSH concentration protected. A similar effect was found for the polyamine, spermidine. In contrast, 0.1 mM L-ergothioneine (2-thiol-L-histidine betaine) exhibited strong protection and 1 mM afforded essentially complete protection. L-Ergothioneine is present in millimolar concentrations in some fungi and is conserved up to millimolar concentrations in critical tissues when consumed by man. L-Histidine and two histidine-containing dipeptides, carnosine and anserine, protected at a concentration of 1 mM, a level at which they are present in striated muscles of various animals.

Endovascular therapy for the carotid blowout syndrome in head and neck surgical patients: diagnostic and managerial considerations.

PURPOSE: To review our institution's recent experience with patients with carotid blowout syndrome who were referred for emergency diagnostic angiography and endovascular therapy. METHODS: Eighteen consecutive patients who had had surgery for cancer of the head and neck and in whom carotid blowout syndrome had occurred were referred to our service in accordance with a standardized protocol. RESULTS: Twenty-three angiographic pathoetiologic conditions were diagnosed in the 18 patients; the majority of these were pseudoaneurysms involving various segments of the carotid system. Multiple lesions were detected in five patients. Most patients were treated by means of permanent balloon occlusion; in 8 patients with either multiple lesions or impending rupture requiring flap reconstruction, a composite permanent balloon occlusion of the affected carotid system was performed. Hyperacute hemorrhages were arrested in all cases. Hemorrhages reoccurred in 2 cases, and in 2 patients who had permanent balloon occlusion of the internal carotid artery, transient ischemic attacks occurred, which appeared to be related to temporary collateral reserve failure. No permanent neurologic complications ensued. CONCLUSION: Our recent experience with carotid blowout syndrome suggests that this clinical diagnosis represents a heterogeneous group of angiographic pathoetiologies that the physician should evaluate carefully before proceeding with endovascular therapy. Specific endovascular approaches depend on the pathoetiologic mechanism of active or impending hemorrhage and the urgency with which intervention is required.

Hypervascular tumor of the buccal space in an adult as a late recurrence of juvenile angiofibroma.

We describe an adult patient with recurrent juvenile angiofibroma, which presented as a rapidly enlarging, hypervascular mass in the anterior part of the cheek. The case is unusual because of the extreme delay (greater than 30 years) and the anatomic location of the recurrence.

Efficacy of transcutaneous computed tomography--guided fine needle aspiration biopsy in patients with laryngeal squamous cell carcinoma, probable failed radiation therapy, and negative transmucosal biopsies.

For patients with suspected recurrent/persistent laryngeal squamous cell carcinoma (SCC) after external beam radiotherapy (EBRT), routine transmucosal biopsies obtained during direct laryngoscopy may fail to reveal active carcinoma. We evaluated transcutaneous computed tomography-guided fine needle aspiration (CTGFNA) in three consecutive patients who had a persistently fixed true vocal fold after EBRT that had been administered for laryngeal SCC and who had multiple negative transmucosal laryngeal biopsies. All three CTGFNA biopsies were positive, but final pathology confirmed invasive SCC in only one of the three patients. Despite its theoretical advantages, CTGFNA in its present form requires further assessment and/or modification.

Management of carotid artery rupture by monitored endovascular therapeutic occlusion (1988-1994).

The reported mortality (40%) and neurologic morbidity (25%) rates for carotid rupture remain unacceptably high. This study was conducted to assess the impact of endovascular detachable balloon occlusion and the changing characteristics of carotid rupture in head and neck surgery. Between January 1, 1988, and June 30, 1994, 18 carotid ruptures were identified in 15 patients. Etiologic factors included radical surgery, radiation therapy, wound complications, and recurrent or persistent carcinoma. In 15 of 18 instances of carotid rupture, patients survived without major neurologic sequelae. After the introduction of endovascular techniques in 1991, the 12 patients whose hemorrhage was definitively managed through permanent balloon occlusion survived without significant neurologic sequelae. Endovascular occlusion techniques in the monitored patient may significantly improve the outcome after carotid rupture.

Computer-aided assessment of bony nasal pyramid dimensions.

OBJECTIVE: To develop a computer-enabled paradigm for assessment of bony nasal pyramid dimensions. DESIGN: Retrospective review of archived computed tomographic data. SETTING: Tertiary level academic center. PATIENTS: Patients who had undergone computed tomographic scans for computer-aided transsphenoidal hypophysectomy were included. Previous nasal surgery, inflammatory sinus disease, and documented maxillofacial trauma were exclusion criteria. INTERVENTION: Archived computed tomographic scan images were reviewed using the software tools on a computer-aided surgical (CAS) system (StealthStation; Sofamor Danek, Memphis, Tenn). Standardized methods for the measurement of nasal bone thickness and bony nasal pyramid projection were established. MAIN OUTCOME MEASUREMENTS: Bony nasal pyramid projection and nasal bone thickness were determined. RESULTS: Computed tomographic scans from 8 patients were reviewed. Nasal bone thickness at the level of lateral osteotomy was 2.39 +/- 0.68 (mean + SD) mm, while nasal bone thickness at the level of intermediate osteotomy was 1.18 + 0.30 mm. Nasal projection from the nasomaxillary suture to the rhinion in the axial plane was 19.20 + 3. 10 (mean + SD) mm, while the corresponding nasal projection at the nasion was 20.61 + 3.52 mm. CONCLUSIONS: This brief report presents a new paradigm for the assessment of the bony nasal pyramid. Additional normative data are necessary. This information has important implications for rhinoplasty instrument design, surgical planning, and aesthetic assessment. It is likely that computer-enabled review of archived computed tomographic images for maxillofacial assessment will become increasingly accepted. Of course, further modifications of computer technology and its specific applications are expected.

Image-guided functional endoscopic sinus surgery.

INTRODUCTION: Computer-aided surgery (CAS) technology in functional endoscopic sinus surgery (FESS) has engendered considerable discussion. OBJECTIVE: The goals of this study were to describe CAS preoperative planning (software-based CT image analysis) and to develop intraoperative CAS strategies for endoscopic sinus surgery. STUDY DESIGN: Between October 1, 1997, and December 31, 1998, the StealthStation (Sofamor Danek, Memphis, TN) was used in 61 FESS cases, and a retrospective review of the findings was performed. The indication for surgery in all instances was chronic rhinosinusitis refractory to medical management. The StealthStation was used to review all CT scans before surgery. Anatomic fiducial registration supplemented by contour mapping was used. RESULTS: Localization accuracy was estimated to be within 2 mm or better. The StealthStation was used for both CT image review and intraoperative localization. CAS was useful in the frontal recess, sphenoethmoid region, posterior ethmoid system, and skull base area. CAS was deemed helpful in situations where the surgical anatomy was altered by previous surgery and extensive inflammatory disease (polyposis, fungal sinusitis, and pansinusitis). CONCLUSION: The paradigm of image-guided FESS surgery, which integrates CAS into FESS, will serve to increase surgical effectiveness and decrease surgical morbidity.

Videoendoscopic analysis of laryngeal function during laughter.

Although commonly encountered in all human cultures, laughter remains poorly understood. In order to examine laryngeal function during laughter, telescopic and fiberscopic videolaryngoscopy was performed on five subjects, who laughed in the different vowels, at various frequencies, and in several voice qualities. During laughter, the vocal folds were found consistently to undergo rhythmic abduction and adduction. At the end of these specific phonation tasks, all subjects were able to gain voluntary control of paramedian vocal fold positioning. This study defined laryngeal function during laughter. These results have important clinical implications. Voluntary vocal fold positioning has important applications in speech therapy for dysphonias, such as vocal fold nodules, in which the primary cause is vocal fold hyperadduction. Patients suffering from these hyperadductive dysphonias may be able to utilize laughter to correct them.

Computer-aided frontal sinus surgery.

Computer-aided surgery technology supports computer-enabled review of CT images and intraoperative surgical anatomy. Many rhinologic surgeons have embraced computer-aided surgery for complicated frontal sinus procedures because computer-aided surgery may simplify these complex procedures. This article discusses the fundamental principles of computer-aided surgery, its limitations, and its application to frontal sinus surgery.

Nonvascularized autogenous bone grafts for craniofacial skeletal augmentation and replacement.

Autogenous nonvascularized bone grafts play an important role in the reconstruction of complex craniomaxillofacial defects. Experimental animal data have demonstrated that grafts from membranous bone donor sites tend to undergo less resorption than grafts from endochondral donor sites, probably because of the different bony architecture of each of these types of grafts. Of all the potential donor sites, the harvest of bone graft from the calvarium is associated with the least overall morbidity. Surgeons should be aware of the biologic basis for the successful application of free autogenous bone grafts.

Advances in postoperative care following functional endoscopic sinus surgery.

The ultimate success of functional endoscopic sinus surgery often is determined during the period of postoperative care. Final surgical results are greatly influenced by preoperative surgical planning and intraoperative decision-making. One goal of postoperative care includes the prevention of scar formation, such as middle turbinate collapse. Specific techniques include mucosal preservation, middle meatal spacer corticosteroids and culture-directed antibiotics.

Revision endoscopic frontal sinusotomy with mucoperiosteal flap advancement: the frontal sinus rescue procedure.

Frontal sinusitis after middle turbinate resection occurs because of stenosis of the frontal ostium by soft tissue scarring or residual bony fragments (which are pulled to the medial orbital wall by scar contracture). Standard endoscopic techniques cannot address this problem; however, revision endoscopic frontal sinusotomy with mucoperiosteal flap advancement (the frontal sinus rescue procedure) relieves this bony stenosis and incorporates a mucosal flap that minimizes postoperative stenosis.

Comparison of Scientific Calipers and Computer-Enabled CT Review for the Measurement of Skull Base and Craniomaxillofacial Dimensions.

Traditionally, cadaveric studies and plain-film cephalometrics provided information about craniomaxillofacial proportions and measurements; however, advances in computer technology now permit software-based review of computed tomography (CT)-based models. Distances between standardized anatomic points were measured on five dried human skulls with standard scientific calipers (Geneva Gauge, Albany, NY) and through computer workstation (StealthStation 2.6.4, Medtronic Surgical Navigation Technology, Louisville, CO) review of corresponding CT scans. Differences in measurements between the caliper and CT model were not statistically significant for each parameter. Measurements obtained by computer workstation CT review of the cranial skull base are an accurate representation of actual bony anatomy. Such information has important implications for surgical planning and clinical research.