Horizontal nystagmus and multiple sclerosis using 3-Tesla magnetic resonance imaging.

BACKGROUND: Nystagmus in patients with multiple sclerosis (MS) is generally attributed to brainstem disease. Lesions in other regions may result in nystagmus. The identification of these other sites is enhanced by using 3-Tesla magnetic resonance imaging (3TMRI) due to increased signal-to-noise ratio. OBJECTIVE: We sought to evaluate the distribution of structural lesions and disruption of tracts in patients with horizontal nystagmus secondary to MS using 3TMRI. METHODS: Twenty-four patients (20 women, 4 men; age range 26-55 years) with horizontal nystagmus secondary to MS underwent 3TMRI brain scans; and 18 patients had diffusion tensor imaging (DTI) for tractography. RESULTS: Nystagmus was bidirectional in 11, right-sided in 6 and left-sided in 7. We identified 194 lesions in 20 regions within the neural integrator circuit in 24 patients; 140 were within the cortex and 54 were within the brainstem. Only two patients had no lesions in the cortex, and 9 had no lesions in the brainstem. There was no relationship between side of lesion and direction of nystagmus. Thirteen of 18 (72 %) had tract disruption with fractional anisotropy (FA) values below 0.2. FA was significantly lower in bidirectional compared to unidirectional nystagmus (p = 0.006). CONCLUSION: In MS patients with horizontal nystagmus, lesions in all cortical eye fields and their descending connections were evident. Technical improvements in tractography may help identify the specific site(s) resulting in nystagmus in MS.

Management of the carotid artery at the skull base.

PURPOSE: To determine appropriate management of benign lesions with significant involvement of the carotid artery at the skull base and present an algorithm for safe treatment of these patients. MATERIALS AND METHODS: From 1982 to 1999, 115 patients with significant parapharyngeal space masses were treated at our institution. Of these patients, 43 had lesions involving the carotid artery at the skull base and served as the basis for this study. All patients underwent preoperative computed tomography or magnetic resonance imaging scans to determine carotid involvement, and all had preoperative 4-vessel arteriograms and carotid occlusion tests with continuous electroencephalography or neurologic examination monitoring to predict safety of carotid sacrifice. RESULTS: Of 43 patients, 41 passed carotid occlusion testing and were treated surgically. Of these patients, 33 (81%) underwent resection of their lesions with preservation of the internal carotid artery, 5 (12%) had resection with bypass or reconstruction of the artery, and 3 (7%) had en bloc resections without artery reconstruction. There were no transient or permanent neurologic sequelae in any patient. CONCLUSIONS: When carotid artery encasement occurs in the setting of benign lesions at the skull base, safe resection with vascular preservation is possible in most cases. If carotid artery resection is necessary, vascular bypass or reconstruction is recommended to minimize neurologic morbidity.

Uncontrolled central adenoid cystic carcinoma: case report.

Central adenoid cystic carcinomas are rare malignancies that are believed to arise in ectopic salivary gland tissue within the maxilla or mandible. We describe the diagnosis and treatment of a central adenoid cystic carcinoma in a 54-year-old man, which we believe was a recurrence of an earlier growth that had not been completely excised. We also present a review of the literature.

Use of computed tomography in the assessment of mandibular invasion in carcinoma of the retromolar trigone.

Carcinomas originating in the retromolar trigone (RMT) are uncommon and characterized by early spread. Determination of mandibular invasion is significant for planning therapy and determining prognosis. For oral cavity cancers in general, CT is reasonably accurate in assessing bone invasion. However, there is a paucity of information specifically addressing the value of CT in the RMT. In this study, the records of patients with biopsy-proven RMT carcinomas treated between 1984 and 1998 were reviewed with attention to preoperative CT scans and histopathologic findings during surgery. Half of the patients who were treated with primary resection had mandibular invasion. Bone invasion was not identified radiographically in 27% of patients with preoperative CT scans. The sensitivity of CT for bone involvement in RMT cancers was 50%, with a negative predictive value of 61.1%. The positive predictive value was 91.1%. These findings suggest that CT is a useful, but potentially inaccurate, predictor of bone invasion in the RMT.

Cyclin D1 (PRAD1, CCND1) and glutathione-S-transferase pi gene expression in head and neck squamous cell carcinoma.

Chromosome 11q13 amplification has been identified in a subset of head and neck squamous cell carcinomas (H&N SCCs). This region contains several putative oncogenes, including cyclin D1 (PRAD1, CCND1), which encodes for an important cell cycle regulatory protein, and the locus encoding for the drug-detoxifying enzyme glutathione-S-transferase-pi (GST-pi). To determine the relationship of cyclin D1 and GST-pi gene amplification to expression of the encoded proteins, the authors examined 64 H&N SCCs by both Southern blot hybridization and immunohistochemistry, using a recently described, affinity-purified, anticyclin D1 polyclonal antibody no. 19 as well as a polyclonal antibody against GST-pi. Anticyclin D1 antibody no. 19 labeled the tumor cell nuclei in 28 (44%) of the H&N SCCs, whereas cytoplasmic immunoreactivity for GST-pi was noted in 55 (86%) neoplasms. By Southern blot 24 tumors (37.5%) showed twofold to tenfold amplification of 11q13 loci; only two of these were coamplified for GST-pi. Immunopositivity with anticyclin D1 antibody no. 19 but not anti-GST-pi significantly correlated with 11q13 amplification (P < .0001). Of the 28 tumors positive with anticyclin D1 antibody no. 19, however, only 18 (64%) were amplified for 11q13, and six amplified tumors did not react with the no. 19 antibody. A strong trend was noted between anticyclin D1 antibody no. 19 reactivity and a hypopharyngeal primary site (P = .053), but no correlations were observed between immunoreactivity and cytological grade, architectural pattern, pathological stage, and disease-free or overall survival. The inconsistent association of cyclin D1 immunoreactivity with 11q13 amplification indicates that other mechanisms may exist for protein overexpression. Immunoreactivity for the GST-pi protein is prevalent in H&N SCC but is clearly unassociated with amplification. In this series, the presence or extent of cyclin D1 and GST-pi immunoreactivity was of no proven prognostic benefit in H&N SCC.

Immunohistochemical staining and Southern blot hybridization for glutathione S-transferase pi in mammary infiltrating ductal carcinoma.

Glutathione S-transferase pi, a drug-detoxifying isoenzyme of potential prognostic value for subsets of patients with mammary cancer, was studied by immunohistochemistry and Southern blot analysis in 58 infiltrating ductal carcinomas. The results were compared with the findings of six important clinicopathologic parameters. Cytoplasmic immunoreactivity for glutathione S-transferase pi was absent in 40%, 1+ in 26%, 2+ in 15%, and 3+ in 19% of the cases. There were no significant correlations between the level of immunostaining and patient age, tumor size, axillary lymph node status, nuclear pleomorphism, or tubule formation, but there was a trend with mitotic count (P = 0.06). Immunoreactivity was associated with histologic grade (P = 0.02) and inversely correlated with estrogen (P = 0.006) and progesterone (P = 0.02) receptor content. Ten percent of the cases showed modest levels of glutathione S-transferase pi gene amplification, but no significant correlations were observed between glutathione S-transferase pi amplification and any of the clinicopathologic parameters or level of immunostaining. The results indicate that increased immunohistochemical staining for glutathione S-transferase pi occurs in high-grade, estrogen and progesterone receptor-negative neoplasms. As glutathione S-transferase pi gene amplification appears unassociated with immunopositivity, other mechanisms are responsible for the production of this isoenzyme in infiltrating ductal carcinomas.

Chromosome 11q13 amplification in head and neck squamous cell carcinoma. Association with poor prognosis.

OBJECTIVE: To determine the clinical and prognostic significance of chromosome 11q13 amplification in squamous cell carcinoma of the head and neck. DESIGN: Retrospective clinical analysis. SETTING: University and private cancer centers. PATIENTS: Fifty-six patients with pathologically confirmed head and neck squamous cell carcinoma whose tumors had been assayed for the presence or absence of chromosome 11q13 amplification. MEASUREMENTS: The degree of DNA amplification in each tumor was determined using chromosome 11q13 probes for the bcl-1 major translocation cluster, PRAD1/cyclin D1 (CCND1), the fibroblast growth factor gene HST1, EMS1, and glutathione-S-transferase-pi-1. The presence or absence of amplification in each patient was correlated with primary site, tumor stage, nodal status, presence or absence of distant metastasis, disease recurrence, time to recurrence, clinical outcome (disease status), and overall survival. RESULTS: Amplification of chromosome 11q13 was identified in 39% (22/56) of patients. Recurrent or persistent disease was identified in 82% (18/22) of cases with amplification and 50% (14/28) of nonamplified cases (P = .04). Mean time to recurrence was shorter in cases with amplification (6.2 months) than those without amplification (10.1 months) (P = .01). Eighteen patients (82%) with amplification and 10 patients (38%) without amplification died of disease or are alive with disease (P = .001). The mean follow-up period was 15.8 months for patients with amplification and 18.6 months for patients without amplification. Overall survival was significantly diminished in patients with amplification (P = .002). Amplification was not related to nodal status, distant metastases, or initial disease stage. CONCLUSIONS: Amplification of chromosome 11q13 loci may be an important biologic marker indicating poor prognosis, independent of clinical stage in head and neck squamous cell carcinoma, and it should be assessed in prospective trials to determine its utility for stratifying treatment and determining prognosis.

Changing the way we talk with elders: promoting health using the communication enhancement model.

Good communication is an essential component of optimal delivery of health care and health promotion efforts. In this article, we address the communication predicament faced by older adults when their opportunities for optimal care are limited by inappropriate communication with formal care providers. We then introduce the Communication Enhancement Model which promotes health in old age by stressing recognition of individualized cues, modification of communication to suit individual needs and situations, appropriate assessment of the health/social problems, and empowerment of both elders and providers. Applications of the Communication Enhancement Model are discussed for two high-risk groups (elders from ethnocultural communities and elders with dementia) to show how it can function as a guide for the development and evaluation of educational interventions with health and social professionals working with elders.

Craniofacial resection at the University of Virginia (1976-1992): survival analysis.

BACKGROUND: The purpose of this study is to evaluate the survival of patients treated at the University of Virginia Health Sciences Center with an anterior craniofacial resection in conjunction with radiotherapy and/or chemotherapy for malignancies of the superior sinonasal cavity. In addition, the impact of aggressive salvage therapy for patients with recurrent disease is considered. METHODS: Between June 1976 and December 1992, a total of 45 patients underwent a craniofacial resection by the Departments of Otolaryngology-Head and Neck Surgery and Neurological Surgery at the University of Virginia. One patient was excluded from the analysis because his neoplasm was benign. Another patient died 2 days postoperatively from multiple strokes. The remaining 43 patients were divided into two subgroups: (1) patients with esthesioneuroblastoma (24 patients) and patients with non-esthesioneuroblastoma malignancies (19). Their survival curves were estimated for the percent survival free of disease by month of follow-up using the product limit of Kaplan and Meier. In addition, the salvage treatment for recurrences was examined for both groups. RESULTS: The 5-year disease-free survival rate for the entire group was 77%, with a 2.3% postoperative mortality. The 5-year disease-free survival for the esthesioneuroblastoma patients was 90%, and that for the non-esthesioneuroblastoma group was 59.1% (p = 0.028). Four of 8 esthesioneuroblastoma patients who recurred and were treated with aggressive salvage therapy were without evidence of disease 5 years after completion of therapy, and 3 of the 10 non-esthesioneuroblastoma patients salvaged were without evidence of disease 57.3 months after therapy (39% surgical salvage). CONCLUSIONS: There is a statistically significant difference between the 5-year disease-free survival for the esthesioneuroblastoma patients and the non-esthesioneuroblastoma patients (90% vs 59.1%; p = 0.028), and aggressive salvage therapy appears to be a more successful option in the esthesioneuroblastoma group of patients.

Cervical manifestations of fibrosing mediastinitis: a diagnostic and therapeutic dilemma.

Fibroinflammatory and fibrosclerosing lesions involving the head and neck outside the thyroid and orbit are exceedingly rare. We present two cases of fibroinflammatory and fibrosclerosing lesions originating in the mediastinum which extended superiorly to involve soft tissues of the neck. These cases indicate that a subset of fibroinflammatory and fibrosclerosing lesions found in the head and neck originate in the mediastinum.

Abnormal nasal glandular secretion in recurrent sinusitis.

Recurrent sinusitis (RS) is a very common clinical problem for which no underlying cause can generally be ascertained. We examined nasal mucosal responses in 14 patients with RS to determine if a relative deficiency in secretion of glandular antimicrobial factors might play a role. Twenty-four subjects with no history of sinusitis were studied concurrently as normal control (NC) subjects. RS was defined by two or more episodes of acute sinusitis per year for 2 or more years. After provocation with 25 mg of methacholine or 1 mg of histamine, nasal washings were analyzed for total proteins: the plasma protein albumin, IgG, and nonsecretory IgA (nsIgA), and the glandular proteins secretory IgA (sIgA), lactoferrin (LFN), and lysozyme (LZM). Although baseline secretions in patients with RS were relatively enriched with LFN and LZM as compared to that of secretions in NC subjects, patients with RS had a blunted cholinergic response with decreased secretion of albumin, IgG, nsIgA, sIgA, and LZM. Histamine responses were equivalent in both patients with RS and NC subjects. After 4 to 12 months of medical treatment, the abnormal cholinergic responses improved on repeat methacholine challenge in all eight subjects with RS rechallenged. Thus, patients with RS have a reversible reduction in nasal mucosal secretory responses to cholinergic stimulation. Since glandular secretions are rich in antimicrobial factors, such as LFN, LZM, and sIgA, it appears possible that the inability to secrete glandular proteins normally may predispose to recurrent infections.

The pathophysiology of rhinitis. III. The control of IgG secretion.

To examine the sources of IgG in nasal secretions, nasal provocation tests with histamine (H) and methacholine (MC) were performed on 22 subjects. Nasal lavages were assayed for IgG, total protein, albumin (Alb), nonsecretory IgA (nonsIgA), and secretory IgA (sIgA). H stimulation dramatically increased the secretion of IgG, nonsIgA, and Alb and also increased the proportion of these proteins compared to total protein. H-induced protein secretion was significantly inhibited by nasal pretreatment with chlorpheniramine maleate but was unaffected by atropine sulfate. sIgA was also stimulated by H challenge, but unlike IgG and other vascular proteins, the proportion of sIgA to total protein (sIgA percent) decreased after H challenges. MC stimulation also increased secretion of IgG, Alb, nonsIgA, and sIgA but did not alter their proportions, compared to total protein. Topical atropine significantly inhibited secretion of all proteins, suggesting a mode of transportation mediated by glandular muscarinic receptor stimulation. Thus, MC can increase the amount of IgG secretion, whereas H increases both the amount and relative proportion of IgG in nasal secretions. These data suggest that pharmacologic stimulation of IgG into nasal secretions may be used as a total to modulate mucosal immunity.

Pathophysiology of rhinitis. Lactoferrin and lysozyme in nasal secretions.

The antimicrobial proteins lactoferrin (Lf) and lysozyme (Ly) are invariably found in nasal secretions. To investigate the cellular sources and the secretory control of these nasal proteins in vivo, 34 adult subjects underwent nasal provocation tests with methacholine (MC), histamine (H), and gustatory stimuli. Nasal lavages were collected and analyzed for total protein (TP), albumin (Alb), Lf, and Ly. MC (25 mg), H (1 mg), and gustatory stimuli (spicy foods) all increased the concentrations of TP, Alb, Lf, and Ly. However, when each protein was assessed as a percentage of TP (i.e., Alb% = Alb/TP; Lf% = Lf/TP; Ly% = Ly/TP), MC and gustatory stimuli, which both induce glandular secretion, selectively augmented Lf% and Ly% without changing Alb%, while H, which primarily increases vascular permeability, increased Alb% without significantly affecting Lf% or Ly%. Gel electrophoresis and immunoblotting analysis of nasal secretions demonstrated both Lf and Ly in cholinergically induced secretions. Furthermore, histochemical analyses of nasal turbinate tissue revealed Lf and Ly colocalization within the serous cells of submucosal glands, providing evidence that both proteins are strictly glandular products within the nasal mucosa. Therefore, both Lf and Ly are produced and secreted from the glands, and their secretion may be pharmacologically regulated in attempts to improve host defenses.

The pathophysiology of rhinitis. II. Assessment of the sources of protein in histamine-induced nasal secretions.

Nasal provocation tests were performed on nine atopic and 15 nonatopic subjects in order to assess the sources of protein in histamine-induced secretions and to examine the bilateral secretory response to unilaterally applied topical histamine (the nasonasal reflex). Nasal lavages were assayed for the following proteins: albumin, total protein, secretory IgA (sIgA), nonsecretory IgA (serum IgA), and total IgA. Histamine stimulation produced a profound ipsilateral protein secretion enriched in the serum proteins albumin and nonsecretory IgA. Histamine also produced a smaller contralateral protein secretion (about 15% as large as the ipsilateral response) which contained disproportionately elevated concentrations of the glandular protein sIgA. Topical pretreatment with chlorpheniramine (an H-1 antihistamine) completely abrogated the ipsilateral nasal secretory response to histamine. Nasal pretreatment with atropine (a muscarinic antagonist) had no significant effect on ipsilateral nasal secretion and did not alter the capacity of histamine to stimulate contralateral secretions (the nasonasal reflex). Histamine therefore stimulates secretion by both a direct action that increases plasma protein extravasation and by an indirect reflex mechanism that stimulates glandular secretion.