A case of asymptomatic gonorrhoea in a male using illegal steroids.

Acute gonococcal urethritis is usually a symptomatic infection in males. Most men will present within one or two weeks after an exposure with symptoms of urethral discharge and dysuria. Early diagnosis is possible in genitourinary medicine clinics with typical signs and symptoms along with microscopy awaiting confirmation by culture and sensitivities. We report a case of gonorrhoea in which we believe the symptoms were masked due to regular use of steroids in a body builder.

Accelerated superfractionated radiotherapy with concomitant boost for locally advanced head-and-neck squamous cell carcinomas.

PURPOSE: A growing body of evidence supports the efficacy of accelerated superfractionated radiotherapy with concomitant boost for advanced head-and-neck carcinomas. This study represents a single-institution experience, performed to identify the factors influencing tumor control, survival, and toxicity. MATERIALS AND METHODS: Between 1988 and 1999, 133 patients with primary squamous cell head-and-neck carcinoma underwent accelerated superfractionated radiotherapy using a concomitant boost. The concomitant boost in this regimen was delivered using reduced fields delivered 3 times weekly in a twice-daily schedule during the final phase. The total radiation dose ranged from 64.8 Gy to 76.5 Gy (mean 71.1). Patients were evaluated in follow-up for local control and late toxicity. Multivariate analysis of treatment and patient parameters was performed to evaluate their influence on toxicity, local control, and overall survival. RESULTS: With a mean follow-up of 37 months, the actuarial overall survival rate for the entire group at 5 years was 24% and the local control rate was 57%. The tumor volume was the most significant predictor of local control, such that each 1-cm(3) increase in volume was associated with a 1% decrease in local control. For patients with tumor volumes 30 cm(3), the 5-year disease-specific survival rate was 52% and 27% (p = 0.004) and locoregional control rate was 76% and 26% (p <0.001), respectively. Seventy-six patients with a minimum of 12 months and median of 39 months toxicity follow-up were studied for late effects. None of these patients experienced Grade 4 or 5 toxicity. The actuarial rate of significant toxicity (Grade III or greater) was 32% at 5 years. Of the toxicities observed, xerostomia (19%) was the most common. Multivariate analysis revealed N stage and dose as independent predictors of Grade 3 effects. CONCLUSION: The locoregional control and survival for patients in this institutional experience compare favorably to other published reports. Tumors of the larynx had the best prognosis. Larger volume tumors were associated with significantly lower local control and survival. Significant late effects were related to dose and nodal status.

Impact of olfactory impairment on quality of life and disability.

OBJECTIVE: To determine whether olfactory loss affects patients' quality of life or level of disability. DESIGN: Retrospective survey using questionnaire data and clinic database review. SETTING: Two university medical center smell and taste clinics. PATIENTS: A total of 1407 patients were tested for smell and taste disturbances from 1984 through 1998. Surveys were mailed to 1093 patients who had abnormal test scores; 420 (38.4%) returned completed surveys. Patients were grouped by self-rated ability to smell as "impaired" (those reporting persisting deficits) or "improved" (those reporting no smell problem when surveyed). MAIN OUTCOME MEASURES: Response frequencies were compared between the 2 groups for questions regarding ability to perform common activities of daily living and quality-of-life issues. RESULTS: Mean (+/-SD) number of activities of daily living affected by olfactory loss was 4.70 +/- 3.56 for the impaired group and 0.61 +/- 1.58 for the improved group (P < .001). Among specific activities, the most common cited impairments were ability to detect spoiled food (impaired vs improved groups, 75% vs 12%; P < .001), gas leaks (61% vs 8%; P < .001), or smoke (50% vs 1%; P < .001); eating (53% vs 12%; P < .001); and cooking (49% vs 12%; P < .001). Differences in quality-of-life issues were reported primarily in the areas of safety and eating. Overall satisfaction with life was reported by 87% of the improved group but only 50% of the impaired group (P < .001). CONCLUSIONS: Patients reporting persistent olfactory impairment after previously documented olfactory loss indicate a higher level of disability and lower quality of life than those with perceived resolution of olfactory compromise.

Olfactory epithelium grafts in the cerebral cortex: an immunohistochemical analysis.

OBJECTIVE: To develop an alternative model for studying the regenerative capacity of olfactory neurons. STUDY DESIGN: An immunohistochemical analysis of mouse olfactory epithelium transplanted to the cerebral cortex. METHODS: Strips of olfactory epithelium removed from donor mice at postnatal day 5 to day 20 were inserted into the parietal cortex of adult mice. Recipient animals were allowed to survive for 25 to 120 days and then perfused with 4% paraformaldehyde 1 hour after bromodeoxyuridine injection. The brains were processed, and frozen sections were obtained. Sections through transplant tissue were analyzed using immunohistochemistry and compared with normal olfactory epithelium. RESULTS: Graft survival approached 85% with mature olfactory neurons detected in 35% of the transplants stained for olfactory marker protein. Transplant epithelium resembled normal olfactory epithelium containing mature olfactory neurons and axon bundles. CONCLUSIONS: Studies of olfactory neuron regeneration have been limited by the inability to produce cultures with long-term viability. Olfactory epithelial grafts to the cerebral cortex provide an alternative approach to the study of olfactory neuron regeneration.

Accuracy, utility, and cost of frozen section margins in head and neck cancer surgery.

OBJECTIVES: Intraoperative frozen section analysis of surgical margins is widely used in head and neck cancer surgery. This study evaluates frozen section accuracy relative to permanent controls and final margins from the entire specimen, the rate at which frozen sections impact intraoperative management, and the resultant cost. STUDY DESIGN: Retrospective. METHODS: From 1997 to 1999 the frozen section results, permanent controls, and final tumor margins from 80 consecutive patients undergoing 420 intraoperative frozen section margins for head and neck malignancy were reviewed. RESULTS: A 98.3% accuracy rate (sensitivity, 88.8%; specificity, 98.9%) was found compared with permanent sections of the same tissue. However, 40% (8 of 20) of patients with positive final margins on the resection specimen, and 100% (15 of 15) with close (<5 mm) margins were not detected by frozen section analysis. The overall accuracy of frozen section in the evaluation of close or positive final margins was 71.3% (sensitivity, 34.3%; specificity, 100%). In addition, 5% (4 of 80) of patients potentially benefited from intraoperative frozen section by virtue of immediate margin revision. The estimated cost of intraoperative frozen section averaged as much as $3,123 per patient, with a cost-benefit ratio of 20:1. CONCLUSIONS: Intraoperative frozen section margins are accurate, but they are costly and cannot reliably eradicate positive final margins. Patients with early-stage lesions and those undergoing re-resection for recurrence or salvage surgery after radiation failure derived the greatest potential benefit from frozen section margins.

Dorsal raphe nuclear stimulation of SCN serotonin release and circadian phase-resetting.

Serotonin (5-HT) is strongly implicated in the regulation of mammalian circadian rhythms. However, little is known of the functional relationship between the circadian clock located in the suprachiasmatic nucleus (SCN) and its source of serotonergic innervation, the midbrain raphe nuclei. In previous studies, we reported that electrical stimulation of the dorsal or median raphe nuclei (DRN and MRN, respectively) induced 5-HT release in the SCN. Notably, DRN- but not MRN-stimulated 5-HT release was blocked by the 5-HT(1,2,7) antagonist, metergoline, suggesting that the DRN signals to the SCN indirectly via the activation of a 5-HT-responsive multisynaptic pathway. In the present study, pretreatment with the 5-HT(2,7) antagonist, ritanserin, also significantly inhibited DRN-electrically stimulated SCN 5-HT release. However, pretreatment with the 5-HT(1A) antagonist, NAN-190, or the 5-HT(2) antagonists ketanserin and cinanserin had little suppressive effect on this DRN-stimulated 5-HT release. In complementary behavioral trials, electrical stimulation of the DRN during subjective midday caused a 1.3-h advance in the free-running circadian activity rhythm under constant darkness, which was inhibited by metergoline. Collectively, these results are evidence that: (1) DRN-stimulated 5-HT release in the SCN requires the activation of an intermediate target with receptors having 5-HT(7) pharmacological characteristics; (2) electrical stimulation of the DRN induces phase-resetting of the circadian activity rhythm; and (3) activation of 5-HT receptors is necessary for this DRN-stimulated circadian phase-resetting. In view of the dynamic changes in DRN neuronal activity incumbent with the daily sleep-activity cycle, and its functional linkages to the SCN and intergeniculate leaflet, the DRN could serve to provide behavioral/arousal state information to various sites comprising the brain circadian system.

Medullary reticular formation activity during ingestion and rejection in the awake rat.

The consummatory components of ingestion and rejection, organized in the caudal brainstem, include licking, swallowing, and the oral phase of rejection (gaping). Studies employing electrical-stimulation induced motor activity have localized interneurons controlling these complex motor patterns to the medullary reticular formation (RF), but the characteristics of these neurons during more naturally induced behavior are unknown. The purpose of the present study was to record the activity profiles of RF neurons during licking, swallowing, and oral rejection in response to gustatory stimulation. Two-hundred and two neurons recorded from awake, freely moving rats were broadly classified as orally related (67%) or non-orally related (33%). Orally related neurons included a large number that were rhythmically active during licking (n = 76; 38%). These "lick-rhythmic" neurons were widely distributed in the RF, but were concentrated in the caudal medullary reticular formation adjacent to the hypoglossal nucleus (Probst's region) and further rostral in the intermediate zone (IRt) of the RF. An analysis of autocorrelations determined that lick-rhythmic neurons in these regions were more closely coupled to licking than to lick-rhythmic neurons more lateral in the parvocellular RF (PCRt). In addition to neurons with weak lick-rhythmic activity, the PCRt also contained a disproportionate number of neurons with orosensory or mixed oro-sensorimotor properties. These data provide evidence for functional specialization within different regions of the medullary RF. A high proportion of lick-rhythmic neurons also showed differential activity associated with swallowing (41%) and/or gaping (75%), further suggesting that the different components of ingestion and rejection share brainstem substrates instead of being produced by unique subsets of interneurons.

In vivo assessment of the midbrain raphe nuclear regulation of serotonin release in the hamster suprachiasmatic nucleus.

Serotonin (5-HT) plays important regulatory roles in mammalian circadian timekeeping; however, little is known concerning the regulation of serotonergic activity in the circadian clock located in the suprachiasmatic nuclei (SCN). By using in vivo microdialysis to measure 5-HT release we demonstrated that electrical or pharmacological stimulations of the dorsal or median raphe nuclei (DRN and MRN, respectively) can alter basal release of 5-HT in the hamster SCN. There were similar increases in SCN 5-HT release after electrical stimulation of either the MRN or DRN, indicating that both could contribute to the serotonergic activity in the SCN. Systemic pretreatment with the 5-HT antagonist metergoline abolished DRN-induced SCN 5-HT release but had little effect on MRN-induced SCN 5-HT release, suggesting different pathways for these nuclei in regulating 5-HT output in the SCN. Microinjections of the 5-HT1A autoreceptor agonist 8-OH-DPAT or antagonist WAY 100635 into the MRN caused significant inhibition and stimulation of SCN 5-HT release, respectively. Both drugs had substantially less effect in the DRN. These differential drug actions indicate that somatodendritic 5-HT1A autoreceptors on MRN neurons provide the prominent raphe autoregulation of 5-HT output in the SCN. Collectively the current results are evidence that DRN as well as MRN neurons can contribute to the regulation of 5-HT release in the hamster SCN. On the basis of the current observations and those from recent anatomic tracing studies of serotonergic projections to SCN it is hypothesized that DRN input to the SCN could be mediated by a DRN --> MRN --> SCN pathway involving a 5-HT-sensitive multisynaptic interaction between the DRN and MRN neurons.

Current treatment practices for early laryngeal carcinoma.

OBJECTIVE: Controversy regarding the management of early laryngeal carcinoma persists in the absence of a definitive comparison of treatment modalities. This study examines the basic management practices for early laryngeal cancer among the American Academy of Otolaryngology-Head and Neck Surgery membership with an emphasis on the role of conservation surgery. METHODS: Questionnaires were randomly distributed to 3000 members with 1000 responses. The results were collated and statistically evaluated with multivariable frequency analysis. RESULTS: For operable supraglottic tumors, supraglottic laryngectomy was advocated by 41.6% of those responding. Definitive radiation therapy was suggested by 5.3% of participants and total laryngectomy by 1.4%. Explanation of treatment options with the patient deciding the therapy was selected by 48.3% of responders. For suitable glottic tumors, hemilaryngectomy was recommended by 37.1%, definitive radiation therapy by 8.1%, total laryngectomy by 1.9%, and patient choice by 50.4% of members completing the survey. When patients were left to weigh the treatment options, surgery was much less likely to be chosen than if it was advocated by the physician. Trends were evident according to practice region and setting, but these variables did not correlate strongly with physician recommendations. However, date of residency completion and rating of available radiation oncology services were significant factors. The evaluation of postoperative considerations in laryngeal conservation surgery demonstrated large variability in the definition of a close margin and the perceived need for additional therapy. CONCLUSIONS: The varied practice patterns among the American Academy of Otolaryngology-Head and Neck Surgery membership reflect the lack of a comparative outcome analysis for the treatment of early laryngeal carcinoma. Consequently, the full reliance on patient choice, which is more pronounced among young physicians, and cost considerations may have the greatest impact on the future treatment of this disease.

Endogenous regulation of serotonin release in the hamster suprachiasmatic nucleus.

Serotonin (5-HT) has been strongly implicated in the regulation of the mammalian circadian clock located in the suprachiasmatic nuclei (SCN). However, little is known of the pattern of neuronal 5-HT release in the SCN or of the factors involved in regulating its release. Using in vivo microdialysis, we demonstrated the existence of a daily rhythm in the output of 5-HT in the SCN of freely behaving hamsters. This rhythm was characterized by a sharp increase in release from a nadir during late midday to peak levels at the light/dark transition. Output declined to basal levels throughout the remainder of the night. A similar pattern also was evident under constant darkness, with increased 5-HT output occurring at the onset of subjective night. Locomotor activity induced by exposure to a novel running wheel had a pronounced phase-dependent effect on 5-HT release in the SCN, with stimulation during the light phase and suppression during the late dark phase. Systemic application of the somatodendritic 5-HT1A agonist BMY 7378 had a significantly greater suppressive effect on 5-HT release in the SCN during the late dark phase compared with mid light phase, indicating that a variation in raphe autoreceptor response may underlie the time-dependent effects of wheel running on 5-HT release. Collectively, these results show that the daily rhythm in output of 5-HT in the SCN is generated endogenously, and that behavioral state can strongly influence serotonergic activity in the circadian clock in a phase-dependent manner.

Lymphatics of the submandibular space: an anatomic, clinical, and pathologic study with applications to floor-of-mouth carcinoma.

The detection and management of submandibular metastases are fundamental to the treatment of oral carcinoma. Detailed investigation of submandibular lymphatic anatomy and subsite predilection for metastases, as well as a comprehensive method for submandibular space dissection, have been lacking. This thesis explores submandibular lymphatic anatomy through a review of the literature and cadaver dissections. A standardized lymph node nomenclature and submandibular dissection technique are proposed. Also presented is a report on 41 consecutive patients with floor-of-mouth squamous cell carcinoma who were prospectively evaluated and treated. Pretreatment clinical and computed tomography (CT) examinations revealed the detection of submandibular metastases to be more difficult than for the remainder of the neck and not improved by the routine use of CT scanning. Management of the neck was either with surgery, which included complete bilateral level I dissections, or at least 2-year follow-up when left untreated. Overall, 39% of patients manifested submandibular disease. The majority of submandibular metastases in this study measured 1 cm or less and most commonly involved the perivascular (primarily prevascular) nodes followed by the preglandular and, previously ill-defined, deep nodes. These findings are discussed with regard to the rationale for currently used neck dissections.

Multicenter, randomized, prospective trial of early tracheostomy.

OBJECTIVES: Determine the effect of early (days 3-5) or late (days 10-14) tracheostomy on intensive care unit length of stay (ICU LOS), frequency of pneumonia, and mortality, and evidence of short-term or long-term pharyngeal, laryngeal, or tracheal injury in head trauma, non-head trauma, and critically ill nontrauma patients. STUDY DESIGN: Randomized, prospective. SETTING: Five Level I trauma centers. METHODS: Data were obtained prospectively and included Acute Physiology and Chronic Health Evaluation III score (AIII), Glasgow Coma Scale score, Emergency Room Trauma Score, Injury Severity Score, Acute Injury Score, type of endotracheal tube or tracheostomy, level of positive end-expiratory pressure, and peak inspiratory pressure. Patients were to undergo laryngoscopy for detection of injury according to the Lindholm criteria at the time of endotracheal tube or tracheostomy removal and be reevaluated at 3 to 5 months after discharge. RESULTS: One hundred fifty-seven patients were entered, 127 to early randomization (3-5 days) and 28 to late randomization (10-14 days); however, only 112 patients with early and 14 with late randomization had completed data forms for the primary study goals. An additional 22 patients from the early entry groups were rerandomized late. Early randomization data: the AIII score was higher (p < 0.05) in the head trauma tracheostomy (65 +/- 4) than in the nontracheostomy group (51 +/- 4) and in the nontrauma tracheostomy (92 +/- 6) than in the nontracheostomy group (68 +/- 7), but was equivalent in the non-head trauma group. Glasgow Coma Scale score, Emergency Room Trauma Score, Injury Severity Score, Acute Injury Score, positive end-expiratory pressure, and peak inspiratory pressure were not significantly different in any of the groups. There were no significant differences in ICU LOS, frequency of pneumonia, or death in any of the groups after either early or late tracheostomy compared with continued endotracheal intubation. Only 83 patients underwent postextubation laryngoscopy. There were no significant differences between the groups; however, there were trends to more vocal cord ulceration and subglottic inflammation in the continued intubation group. No patient was seen in this study with late vocal cord or laryngeal stenosis; there were no tracheal-innominate artery fistulae. Seven of the patients with abnormal findings at extubation had normal 3- to 5-month postextubation laryngoscopy. CONCLUSION: Physician bias limited patient entry into the study. Although there were higher AIII scores in the head trauma early tracheostomy patients, there were no differences in the primary end points of ICU LOS, pneumonia, or death in any of the groups studied. Long-term endoscopic follow-up was poor, but no known late tracheal stenosis was seen.

Motor and premotor mechanisms of licking.

The location, organization and anatomical connections of a central pattern generator (CPG) for licking are discussed. Anatomical and physiological studies suggest a brainstem location distributed within several subdivisions of the medullary reticular formation (RF). The involvement of widespread RF regions is evident from brainstem recording experiments in awake freely moving preparations and studies employing electrical stimulation of the frontal cortex to produce ororhythmic activity. The complex multifunctional properties of RF neurons producing licking are indicated by their activity during licking, swallowing and the rejection of an aversive gustatory stimulus. Anatomical studies place descending inputs to a brainstem CPG for licking to widely distributed areas of both the medial and lateral RF. In contrast, most projections originating from brainstem orosensory nuclei terminate primarily within the lateral RF. Because many pre-oromotor neurons appear concentrated largely in the intermediate zone of the RF (IRt), it is hypothesized that neurons from both lateral and medial sites converge within the IRt to control oromotor function.

Factors affecting smoking cessation in patients with head and neck cancer.

The role of tobacco in the etiology of upper aerodigestive tract carcinomas is well established. Smoking decreases the effectiveness of cancer therapy and increases the risk of all treatment modalities. Smoking adversely affects the general health of the cancer survivor and places the patient at risk of developing additional primary tumors. The smoking habits of head and neck cancer patients were evaluated using a questionnaire administered at two tertiary head and neck cancer centers. Demographic factors, level of exposure, tumor stage and location, treatment modalities, concomitant alcohol use, and cessation methods were examined. Results demonstrate a high rate of smoking cessation at the time of cancer diagnosis. Significant demographic factors were not identified. Physical barriers to continued smoking because of cancer treatment as well as counseling at the time of tumor diagnosis were the most effective deterrents to continued tobacco use. Heavy alcohol use was a negative predictor of smoking cessation. Pharmacologic aids alone were found to be of no value. This study demonstrates the difficulties with smoking cessation in head and neck cancer patients, and emphasizes the importance of intervention by the otolaryngologist-head and neck surgeon.

Distribution of fos-like immunoreactivity in the medullary reticular formation of the rat after gustatory elicited ingestion and rejection behaviors.

The distribution of neurons in the medullary reticular formation (RF) activated by the ingestion of sucrose or rejection of quinine was examined using standard immunohistochemical techniques to detect the expression of the Fos protein product of the immediate-early gene c-fos. Double-labeling techniques were used to gain further insight into the possible functional significance of RF neurons exhibiting Fos-like immunoreactivity (FLI). Compared with sucrose and unstimulated controls, quinine elicited significantly more FLI neurons in three specific RF subdivisions: parvocellular reticular nucleus (PCRt), intermediate reticular nucleus (IRt), and dorsal medullary reticular nucleus (MdD). Moreover, the number of FLI neurons in the RF of quinine-stimulated animals was significantly correlated with the degree of oromotor activity. Thus, the distinct distribution of FLI neurons throughout the RF after quinine may reflect the activation of a specific oral rejection circuit. The double-labeling results indicated a high degree of segregation between FLI neurons and premotor projection neurons to the hypoglossal nucleus (mXII) retrogradely labeled with Fluorogold. Thus, although there were a significant number of double-labeled neurons in the RF, the major concentration of premotor projection neurons to mXII in IRt were medial to the preponderance of FLI neurons in the PCRt. In contrast, there was substantial overlap between FLI neurons in the RF and labeled fibers after injections of the anterograde tracer, biotinylated dextran into the rostral (gustatory) portion of the nucleus of the solitary tract. These results support a medial (premotor)/lateral (sensory) functional topography of the medullary RF.

Management of malignant schwannomas of the paranasal sinuses and anterior skull base.

The evolution of skull base surgery has facilitated the extirpation of previously unresectable tumors. As experience with skull base surgery increases, the feasibility of resection and long-term outcomes is becoming apparent for the more common lesions. Neoplasms such as malignant schwannomas are rare and, therefore, defy single-institution analysis. The treatment and four-year follow-up of a malignant paranasal sinus and anterior skull base schwannoma is described. Analysis of the literature confirms the low incidence of this tumor and supports the efficacy of skull base surgery in its treatment.