The effect of corticosteroids in the treatment of experimental sinusitis

Emerging evidence indicates that medically recalcitrant sinusitis may be associated with a prolonged and excessive state of inflammation rather than a simple bacterial infection. Corticosteroids have been anecdotally reported to be helpful in treating patients with sinusitis; however, there are no scientific studies documenting the safety and efficacy of corticosteroid therapy in sinusitis. To resolve the controversy over whether corticosteroids promote or inhibit the resolution of sinusitis, we present a prospective study of 80 rabbits with surgically introduced pseudomonal sinusitis that were then treated in one of four arms: control, ceftazidime, methylprednisolone, and ceftazidime with methylprednisolone. Sinus cavities were then evaluated after 5, 14, 21, and 28 days of treatment both by histologic inflammation grading and bacterial quantification. Results showed a significant decrease in bacterial loads in both the antibiotic and antibiotic with steroid arms over control animals, although no difference was seen between the two. Histologic grading showed a similar trend, although statistical significance was not obtained. Overall, this study demonstrated no clear advantage of steroids in the treatment of sinus infections using this model. At the same point, no significant reduction in the effectiveness of antibiotic therapy was seen with concurrent steroid use. A number of limitations of the animal model are noted and the need for human studies in this area is discussed.     

Pressure-sensitive and -insensitive coupling in gamma-aminobutyric acid(A) receptors

RATIONALE: Previous behavioral and biochemical studies suggest that allosteric coupling processes initiated by benzodiazepines, barbiturates and neuroactive steroids can be sub-categorized on the basis of their sensitivities to antagonism by increased atmospheric pressure. However, biochemical evidence supporting this hypothesis was limited to single concentration studies in long sleep (LS) mice. OBJECTIVE: The present paper addresses these issues by extending biochemical investigation of pressure effects on allosteric modulators across a range of concentrations that allosterically enhance gamma-aminobutyric acid (GABA)A receptor function and alter behavior using two mouse genotypes. In addition, the effects of pressure on ligand binding were explored to further investigate the mechanism of pressure antagonism of allosteric modulation. METHODS: The effects of 12 times normal atmospheric pressure (ATA) of helium-oxygen gas (heliox) on allosteric modulation of GABA(A) receptor function and [3H]flunitrazepam binding was tested in LS and C57BL mouse brain membranes (microsacs) using chloride flux and high-affinity binding assays. RESULTS: In both genotypes, exposure to 12 ATA heliox antagonized the allosteric enhancement of GABA(A) receptor function by flunitrazepam (0.1-10 microM) and pentobarbital (0.1-50 microM) but did not affect allosteric modulation by 3alpha-hydroxy-5beta-pregnan-20-one (0.1-1 microM). Pressure did not affect benzodiazepine receptor affinity (Kd) or the number of benzodiazepine receptors (Bmax). CONCLUSIONS: The results: (1) confirm that there are differences in sensitivity to pressure antagonism of allosteric coupling among GABA(A) allosteric modulators; (2) demonstrate that these differences are not concentration or genotype dependent; (3) add evidence that pressure antagonizes allosteric modulation by uncoupling the receptor and (4) support the hypothesis that allosteric modulation of receptor function can be sub-categorized on the basis of sensitivity to pressure antagonism.     

Extracardiac vasculature in candidates for Fontan surgery: MR imaging

Magnetic resonance (MR) imaging was performed in 53 patients considered to be candidates for a modified Fontan operation to repair cardiac or extracardiac vascular anomalies. The MR studies were reviewed retrospectively, and the findings with regard to the extracardiac vascular anatomy were compared with the findings from angiography or surgery. The accuracy of MR for the correct identification of the systemic veins was 98%; for pulmonary arteries, 97%; and for pulmonary veins, 95%. For identification of pulmonary veins, MR imaging had a sensitivity of 90% and a specificity of 100%. MR provides excellent demonstration of the extracardiac vascular structures, which are of particular importance in patients being considered for a Fontan procedure.     

Functional endoscopic sinus surgery in aviators with recurrent sinus barotrauma

Recurrent sinus barotrauma in an aviator is difficult to treat successfully. Exacerbations frequently result in marked aviator discomfort, cycles of temporary restriction from aviation duties, or even permanent disqualification for flying duties. Medical management and standard sinus operations are often ineffective, seldom curative, and have a disappointing record in returning the aviator to flying duties. Detailed computerized tomographic scanning of the paranasal sinuses coupled with the functional endoscopic sinus surgery approach directs treatment at the causative pathology. Sinus ventilation is improved while making possible a return to active flight status without recurrence of sinus barotrauma. Initial experience with the functional endoscopic sinus surgery technique in such a patient population is reported. A discussion of recurrent sinus barotrauma, paranasal sinus anatomy, and the theory of endoscopic surgical management for sinus disease is included.