Diazepam tolerance effects on vestibular function testing, Part I: Saccadic parameters during electronystagmography.

OBJECTIVES: Benzodiazepines, particularly diazepam (DZ), are used in clinical practice to suppress acute vestibular symptoms. There have been limited studies looking at the effects of tolerance to DZ on parameters designed to measure the integrity of the vestibular system and its interaction with the oculomotor and balance systems. METHODS: In a double-blinded, repeated-measures design, we randomized 30 young healthy men into one of two treatment groups (diazepam and placebo) and assessed with electro-oculography the effects of clinical divided doses of DZ on saccadic eye movements and sedation over 16 days. RESULTS: Only sedation and saccadic latency were significant (p < .05) for treatment group, indicating selective effects on different central nervous system mechanisms. No significant effect for time was seen in any of the variables measured. Bonferroni t-test comparisons of the DZ group among 3 days were significant (p < .017) between baseline and day 3 for saccadic latency and accuracy and between day 3 and day 16 for self-ratings of sedation. CONCLUSIONS: Saccadic latency and accuracy and sedation ratings appear to be more sensitive to changes over time and less affected by subject variability than saccadic eye velocity. It remains questionable whether patients who have been on DZ for acute or extended periods of time need to discontinue the drug 48 hours before testing.

Diazepam tolerance effects on vestibular function testing, part II: vestibulo-ocular reflex parameters during rotational testing.

OBJECTIVES: The purpose of this prospective study was to determine whether clinical doses of diazepam (DZ; 10 mg/d) administered for 14 days result in tolerance as measured by the sinuosidal harmonic acceleration (SHA) rotational test. It has been shown that repeated dosing with DZ leads to accumulation and tolerance in outcome measures that assess memory, sedation, and psychomotor tasks. METHODS: In a double-blinded, repeated-measures design, 30 normal male subjects who ranged in age from 20 to 36 years were randomly assigned to a placebo group or a DZ group and participated in 6 SHA rotational sessions over a 2-week period. Analysis of drug-placebo differences in percent change from baseline was performed with a 1-way analysis of variance. RESULTS: Vestibulo-ocular reflex gain and phase frequencies at 0.01, 0.02, 0.04, and 0.08 Hz were significant (p < .05) for treatment group. No significant effect was observed for gain and phase frequency at 0.16 Hz--a finding that indicates selective effects on different central nervous system mechanisms. There was no statistical significance for time. CONCLUSIONS: Clinically, the DZ subjects' scores remained within the normal ranges for vestibulo-ocular phase and gain, suggesting that patients in whom drug cessation is problematic may not have to discontinue DZ before testing with the SHA rotational system.

Molecular responses of vascular smooth muscle cells to paclitaxel-eluting bioresorbable stent materials.

We studied the influence of paclitaxel, eluted from poly(L-lactic acid) (PLLA), on cultured vascular smooth muscle cell (VSMC) proliferation as a model of bioresorbable stent-induced restenosis. We blended paclitaxel in cast PLLA films (P-PLLA), demonstrating controlled release of the drug, then studied VSMC adhesion, proliferation, and gene expression profiles. No difference in cell adhesion was found between P-PLLA and PLLA controls (105 +/- 12% of PLLA controls). However, P-PLLA significantly reduced VSMC proliferation (40 +/- 15% of PLLA controls, p < 0.05). Using cDNA microarray technology, we identified major effects of P-PLLA, including: upregulation of genes related to apoptosis, anti-proliferation and antioxidation; and suppression of cell cycle regulators and cell survival markers. The expression patterns indicate that P-PLLA regulates gene expression and cell functions via new pathways, including receptor tyrosine kinase (RTKs), mitogen-activated protein kinase (MAPKs), and protein kinase (PKs, e.g., PKA) pathways, in addition to the stabilization of polymerized-microtubules.

Clinical presentation of allergic fungal sinusitis in children.

OBJECTIVE: To compare the differences in the clinical and radiographic presentation of allergic fungal sinusitis in children and adults. STUDY DESIGN: Retrospective chart and computed tomography review. METHODS: The settings included a tertiary care children's hospital, adult academic private hospital, and academic affiliated county hospital. All patients with documented allergic fungal sinusitis who underwent computed tomography evaluation and had surgical treatment of their disease from 1988 to 1999 were included in the study. In total, 151 patients aged 5 to 75 years; 44 of these patients were less than or equal to 17 years of age (children) and 107 were greater than 17 years of age (adults). Main outcome measures included 1) the presence of obvious bony facial abnormalities on presentation, 2) bilateral or unilateral sinus disease on presentation, 3) the presence of asymmetrical disease on presentation, 4) the presence of bony extension on computed tomography scan, and 5) type of fungus present. RESULTS: Fifteen of 36 (42%) pediatric patients and 10 of 103 (10%) adult patients had obvious alteration of their facial skeleton (proptosis, telecanthus, or malar flattening) on presentation (P <.05). Proptosis was the most common facial abnormality in both groups and was seen more often in children (8 of 36 [22%]) than in adults (9 of 103 [9%]) (P <.05). Twenty-eight of 40 (70%) pediatric patients and 37 of 100 (37%) adult patients presented with unilateral sinus disease (P <.05). Thirty-five of 40 (88%) pediatric patients and 58 of 100 (58%) adults presented with asymmetrical disease (P <.05). Computed tomography scans showed that 10 of 40 (25%) pediatric patients and 23 of 100 (23%) adult patients had bony erosion with extension of disease into surrounding structures (P >.05). Cultures from both adults and children showed mainly Bipolaris and Curvilaria species in equal amounts (P >.05). Adults had a greater incidence of Aspergillus species. CONCLUSIONS: Presentation in pediatric patients with allergic fungal sinusitis is different from that in adults, with children having obvious abnormalities of their facial skeleton, unilateral sinus disease, and asymmetrical disease more often. Findings on computed tomography scan show an equal amount of bony erosion with extension of disease. The types of fungus cultured in the sinus cavities are similar in both groups.

Suppurative complications of acute otitis media in the era of antibiotic resistance.

OBJECTIVE: To review our experience with suppurative complications of acute otitis media (AOM) in the era of antibiotic resistance, given a perceived increase in the number of such cases in recent years requiring surgical intervention. DESIGN: Retrospective review of pediatric patients presenting with suppurative complications of AOM from January 1993 to June 2000. SETTING: Academic tertiary care children's medical center. PATIENTS: A total of 90 pediatric patients, ranging in age from 3 months to 16 years (mean age, 45 months). RESULTS: A total of 104 suppurative complications of AOM occurred in 90 patients over the 7.5-year study period. The incidence of noncoalescent, coalescent, and total cases of mastoiditis and total number of suppurative complications all increased over the study period, with coalescent outpacing noncoalescent disease during the last 3 years of the study. A trend toward an increasing number of cases requiring surgical intervention was noted during the study period, corresponding to an increasing number of resistant Streptococcus pneumoniae isolates. Ten of 16 S pneumoniae isolates were resistant, primarily collected from younger children ranging in age from 4 to 24 months (mean age, 11.9 months). CONCLUSION: The rising incidence of resistant S pneumoniae corresponded to the increasing number of suppurative complications of AOM during the study period and seemed to contribute to more aggressive infectious processes requiring surgical intervention.

Protein-loaded bioresorbable fibers and expandable stents: Mechanical properties and protein release.

There is an increasing interest in bioresorbable polymeric stents for coronary, urethral and tracheal applications. These stents can support body conduits during their healing process and release biologically active agents from an internal reservoir to the surrounding tissue. A removal operation is not needed. Bioresorbable poly(L-lactic acid) fibers were prepared through melt spinning accompanied by a postpreparation drawing process. Novel expandable bioresorbable stents were developed from these fibers. Bioresorbable microspheres containing albumin were prepared and attached to the stents, to serve as a protein reservoir coating. The controlled release of albumin from the microsphere-loaded stent was studied. The fibers combine high strength and modulus, together with good ductility and flexibility. An increase in draw ratio increases the tensile strength and modulus and decreases the ultimate strain. The stents demonstrated excellent initial radial compression strength and good in vitro degradation resistivity, which makes them applicable for supporting blood vessels for at least 20 weeks. Microspheres bound to these stents enable effective protein loading, without reducing the stent's mechanical properties. The protein release from the microsphere-loaded stent occurs by diffusion, is determined mainly by the initial molecular weight of the bioresorbable polymer and its erosion rate, and is strongly affected by the microsphere structure.

Natural history of allergic fungal rhinosinusitis: a 4- to 10-year follow-up.

BACKGROUND: Numerous studies have noted the high rate of recidivism after the initial treatment of allergic fungal rhinosinusitis (AFS). Short-term studies have revealed varying recurrence rates based on therapy; however, little is currently known about the long-term natural history of the disease. OBJECTIVE: Our goal was to address the question of long-term outcomes in AFS patients and make observations about the natural history of the disease. PATIENTS AND METHODS: Seventeen patients with follow-up ranging from 46 to 138 months were examined and interviewed, and their charts were reviewed. A quality-of-life survey was completed, and blood was drawn to measure immunoglobulin levels. RESULTS: All patients initially underwent treatment with a combination of surgery, systemic and/or topical corticosteroids, and immunotherapy to pertinent fungal and nonfungal antigens. Normalization of sinonasal mucosa (Kupferberg stage 0) was seen in 5 (29%) of 17 patients, whereas 76% demonstrated either normal or slight mucosal edema (Kupferberg stage 0 or 1). Serologic testing revealed fungus-specific IgE significantly elevated in all 17 patients. CONCLUSION: The initial choice of therapy did not appear to affect the long-term outcome, and patients tended to be doing well overall. These results suggest that after successful initial treatment and control of AFS, many patients can achieve a quiescent disease state.

Skull base cerebrospinal fluid fistulas: a comprehensive diagnostic algorithm.

OBJECTIVE: Our goal was to assess the efficacy of current diagnostic modalities in the management of skull base cerebrospinal fluid (CSF) fistulas. METHODS: We conducted a retrospective review of all patients presenting to our institution over the past 6 years with skull base CSF fistulas. RESULTS: Fifty-two patients were included in the study. beta2-Transferrin analysis of collected specimen was the most efficacious means of confirming a CSF leak. High-resolution computed tomography was the most informative radiographic study, yielding a sensitivity and an accuracy of 87%. Magnetic resonance cisternography, yielding a sensitivity and an accuracy of 78%, was instrumental in localizing the site of leak for a few cases but was most commonly corroborative. Using a graduated diagnostic approach, successful repair was attained in 88% of cases after 1 attempt and 98% after 1 or 2 attempts. CONCLUSION: For patients with skull base CSF fistulas, a graduated diagnostic approach with emphasis on confirmation of leak by beta2-transferrin analysis and precise localization by high-resolution computed tomography is both efficacious and cost effective.