Faculty Bibliography

Low birth weight is a risk factor for the subsequent development of hypertension in humans. We previously reported that reduced uterine perfusion in the pregnant rat results in growth-restricted offspring predisposed to the development of hypertension. The purpose of this study was to determine whether the sympathetic nervous system plays a role in mediating hypertension in this model of low birth weight. Weight at birth was significantly decreased in male growth-restricted offspring (5.9+/-0.1 grams) as compared with male control offspring (6.5+/-0.2 grams; P<0.05). At 10 weeks of age, growth-restricted offspring and control offspring were randomly assigned to either an intact group (sham-denervated) or a group subjected to bilateral renal denervation. For sham-denervated offspring, mean arterial pressure was significantly elevated in growth-restricted offspring (145+/-4 mm Hg; n=7) as compared with control offspring (134+/-3 mm Hg; P<0.05; n=9) at 12 weeks of age. Bilateral renal denervation resulted in a marked reduction in arterial pressure in growth-restricted offspring (125+/-3 mm Hg; P<0.01; difference of 20 mm Hg versus sham growth-restricted; n=8) but no significant decrease in control offspring (127+/-3 mm Hg; difference of 7 mm Hg versus sham control; n=9). Adequacy of renal denervation was verified by >90% reduction in renal norepinephrine content. Therefore, these findings indicate the renal nerves play an important role in mediating hypertension in adult growth-restricted offspring.

To report one patient with an ectopic salivary tissue tag on the tonsil, and review the embryology, management, and implications of this benign disorder. Case report with literature review. Ectopic salivary tissue presented on the tonsil of a child as a painless, growing, unilateral pale exophytic mass. Tonsillectomy was performed to provide diagnosis, and was curative. Ectopic salivary tissue of the tonsil is a rare finding. Tonsillectomy allows for definitive diagnosis and treatment

OBJECTIVE:To report a multiinstitutional experience of men presenting with infertility secondary to inguinal hernia repair using polypropylene mesh. SUMMARY BACKGROUND DATA/BACKGROUND:An estimated 80% of inguinal hernia operations involve placement of a knitted polypropylene mesh to form a "tension-free" herniorrhaphy. The prosthetic mesh induces a chronic foreign-body fibroblastic response creating scar tissue that imparts strength to the floor and leads to fewer recurrences. However, little is known about the long-term effects of the polypropylene mesh on the vas deferens, especially with regard to fertility. METHODS:Eight institutions in the United States reported a total of 14 cases of azoospermia secondary to inguinal vasal obstruction related to previous polypropylene mesh herniorrhaphy. Patient characteristics and operative findings were forwarded to 1 center for tabulation of data. RESULTS:Mean patient age was 35.5 years with an average duration of infertility of 1.8 years. Mean number of years between urologic evaluation and herniorrhaphy was 6.3 years. Types of inguinal hernia repair previously performed were: open (10), laparoscopic (2), or both (2). Nine patients had bilateral obstruction and 5 patients had unilateral obstruction with contralateral testicular atrophy or epididymal obstruction. Surgical exploration revealed a dense fibroblastic response encompassing the polypropylene mesh with either trapped or obliterated vas in all patients. Surgical reconstruction was performed in 8 of 14 men (57%). CONCLUSION/CONCLUSIONS:Reconstruction to restore fertility can be difficult secondary to fibrotic reaction. Before undergoing polypropylene mesh herniorrhaphy, men, especially of young reproductive age or with a solitary testicle, need to be carefully advised of potential obstruction and compromise to future fertility.

In the neocortex, each neuron receives thousands of synaptic inputs distributed across an extensive dendritic tree. Although postsynaptic processing of each input is known to depend on its dendritic location, it is unclear whether activity-dependent synaptic modification is also location-dependent. Here we report that both the magnitude and the temporal specificity of spike-timing-dependent synaptic modification vary along the apical dendrite of rat cortical layer 2/3 pyramidal neurons. At the distal dendrite, the magnitude of long-term potentiation is smaller, and the window of pre-/postsynaptic spike interval for long-term depression (LTD) is broader. The spike-timing window for LTD correlates with the window of action potential-induced suppression of NMDA (N-methyl-D-aspartate) receptors; this correlation applies to both their dendritic location-dependence and pharmacological properties. Presynaptic stimulation with partial blockade of NMDA receptors induced LTD and occluded further induction of spike-timing-dependent LTD, suggesting that NMDA receptor suppression underlies LTD induction. Computer simulation studies showed that the dendritic inhomogeneity of spike-timing-dependent synaptic modification leads to differential input selection at distal and proximal dendrites according to the temporal characteristics of presynaptic spike trains. Such location-dependent tuning of inputs, together with the dendritic heterogeneity of postsynaptic processing, could enhance the computational capacity of cortical pyramidal neurons

Inducible nitric oxide synthase (iNOS) is responsible for generating high levels of nitric oxide (NO) in tissues. Increased iNOS expression has been demonstrated in a number of carcinomas including head and neck squamous cell carcinoma (SCC). However, iNOS levels have not been evaluated specifically in oral cavity SCC, or in the precancerous lesions that progress to oral SCC. Also, NO levels have not been measured in oral precancerous or cancerous tissues. We therefore measured iNOS mRNA, iNOS protein and NO in oral SCC, oral dysplasias and normal oral epithelium. We used RT-PCR to quantify and compare iNOS mRNA levels in these oral tissue specimens. We found that iNOS mRNA was overexpressed in 41% of oral SCC but in only 8% of dysplasia specimens (P = 0.003). Immunohistochemistry was used to evaluate iNOS protein levels in oral SCC, oral dysplasias and normal oral epithelium. A significantly higher percentage of oral SCC specimens showed the highest level of iNOS staining relative to the oral dysplasias and normal oral epithelial samples (95% of oral SCC, 50% of dysplasias, and only 0% of normal epithelial controls, P < 0.0001). The positive staining for iNOS was limited to the SCC cells. Production of NO from iNOS was quantified using HPLC and found to be significantly higher in oral SCC (1.45 +/- 0.56 microg/ml) than normal epithelial controls (0.43 +/- 0.26 microg/ml) (P = 0.0013). We conclude that iNOS mRNA levels and NO production are significantly increased, in oral SCC compared to oral dysplasias and normal epithelial controls. These findings suggest that increased iNOS expression and the generation of high NO levels might have a role in oral SCC development

OBJECTIVE: To statistically analyze the long-term results of alar base reduction after rhinoplasty. METHODS: Among a consecutive series of 100 rhinoplasty cases, 19 patients required alar base reduction. The mean (SD) follow-up time was 11 (9) months (range, 2 months to 3 years). Using preoperative and postoperative photographs, comparisons were made of the change in the base width (width of base between left and right alar-facial junctions), flare width (width on base view between points of widest alar flare), base height (distance from base to nasal tip on base view), nostril height (distance from base to anterior edge of nostril), and vertical flare (vertical distance from base to the widest alar flare). Notching at the nasal sill was recorded as none, minimal, mild, moderate, and severe. RESULTS: Changes in vertical flare (P<.05) and nostril height (P<.05) were the only significant differences seen in the patients who required alar reduction. No significant change was seen in base width (P=.92), flare width (P=.41), or base height (P=.22). No notching was noted. CONCLUSIONS: It would have been preferable to study patients undergoing alar reduction without concomitant rhinoplasty procedures, but this approach is not practical. To our knowledge, the present study represents the most extensive attempt in the literature to characterize and quantify the postoperative effects of alar base reduction

BACKGROUND: Anatomic and mucosal obstruction of the frontal sinus outflow tract (FSOT) can result in frontal sinusitis often associated with frontal headache. Thorough evaluation of symptomatic patients requires axial and coronal computerized tomographic (CT) scans of the paranasal sinuses (PNS). With the advent of multichannel multidetector CT scanning, the availability of high-quality sagittal images has become increasingly widespread. However, the utility of these images in the assessment of FSOT patency has not yet been established. METHODS: A retrospective review of coronal and sagittal images from 25 PNS CT scans (50 sides) were randomized, blinded, and independently evaluated by two neuroradiologists. FSOT obstruction by agger nasi cells, the ethmoid bulla, and mucosal disease was assessed. A degree of confidence was rendered for each of these findings. The results were then compared against a consensus diagnosis, which was rendered based upon simultaneous reading of the coronal and sagittal images. Generalized estimating equations were used to assess the difference between sagittal and coronal images in terms of reader confidence and diagnostic concordance with the consensus. RESULTS: Review of sagittal images had a higher degree of concordance with the consensus than did coronal images, and was highest for mucosal disease. Both readers were more confident in rendering a diagnosis based upon the sagittal images. CONCLUSION: Sagittal reformatted CT images of the PNS are helpful in the radiologic evaluation of the FSOT. Experienced neuroradiologists had a higher degree of confidence in the diagnosis of the obstruction of the FSOT using sagittal reformatted images

Functional imaging has become an increasingly important diagnostic tool for head and neck cancer, and as its availability increases so will its utilization. Positron emission tomography (PET) with the radiotracer 18-fluorodeoxyglucose (18FDG) is the most commonly used functional imaging technology, and it has the potential to improve the staging and detection of head and neck tumors compared with conventional cross-sectional imaging techniques such as CT or magnetic resonance imaging. Specifically, PET contributes valuable information for localizing a primary tumor in patients with an unknown primary and neck metastasis, in the staging of untreated head and neck cancer, in the detection of residual disease after definitive radiotherapy or chemoradiotherapy, and in the detection of recurrent disease. New technologies have been introduced using the combination of CT and PET, which allows exact anatomic correlation with areas of increased tracer uptake. In addition, new tracers may allow quantification of important cellular processes related to tumor proliferation or identification of tumors that may respond to certain targeted therapies. This strategy will eventually enable physicians to tailor therapy to molecular characteristics and therefore improve outcomes for patients with head and neck cancer

Beta-6 Integrin, tenascin-C, and MMP-1 (matrix metalloproteinase-1) are invasion-related proteins that are frequently overexpressed in many human malignancies. The objective of this study was to determine whether there is overexpression of these molecules in three types of salivary neoplasms showing markedly different behavior. A total of 55 formalin-fixed, paraffin-embedded archived specimens comprising 19 adenoid cystic carcinomas (ACC), 18 polymorphous low-grade adenocarcinomas (PLGA) and 18 pleomorphic adenomas (PA) were utilized in this study. A standard immunohistochemical technique was used to determine the expression levels of beta-6 integrin, tenascin-C, and matrix metalloproteinase-1 (MMP-1) proteins. Sections were assessed semiquantitatively, and tumors were divided into two groups, low-expressors (0-1+) and high-expressors (2-3+) for statistical analysis. Staining was graded as 0 (<1% positive tumor cells), 1+ (<25% positive tumor cells), 2+ (25-50% positive tumor cells), and 3+ (>50% positive cells). The results showed that the malignant tumors were higher expressors of beta-6 than the benign tumors. ACCs showed significantly higher expression of beta-6 than PAs (p=0.04). No significant difference was observed between ACCs and PLGAs. beta-6 expression was rarely seen in normal salivary gland epithelium and was occasionally present in mucosa overlying the tumors. PAs were high-expressors of tenascin-C with a significant difference relative to ACCs (p=0.03). A majority of tumors in all three tumor types showed high expression of MMP1 with expression significantly greater in the PAs compared to ACCs (p=0.008). We conclude that ACCs and PLGAs express beta-6, tenascin-C, and MMP-1, but that their expression patterns are not significantly different. beta-6 appears to be more closely associated with the malignant tumors, and MMP-1 more closely associated with the benign tumors. We believe that beta-6, tenascin-C, and MMP-1 proteins are part of the molecular repertoire used by salivary tumors for malignant invasion and benign tumor expansion