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Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa occurs remains largely undefined.Twenty subjects undergoing functional endoscopic sinus surgery (FESS) for CRS were randomized to one of two groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal mucus, sinonasal tissues and serum at steady state.Doxycycline concentrations measured in the mucus were significantly lower compared to that in the serum (mean mucus/serum ratio = 0.16, p p p = 0.002) and the tissue (mean mucus/tissue ratio = 0.60, p Although the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complexity of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS. Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa occurs remains largely undefined. Twenty subjects undergoing functional endoscopic sinus surgery (FESS) for CRS were randomized to one of two groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal mucus, sinonasal tissues and serum at steady state. Doxycycline concentrations measured in the mucus were significantly lower compared to that in the serum (mean mucus/serum ratio = 0.16, p p p = 0.002) and the tissue (mean mucus/tissue ratio = 0.60, p Although the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complexity of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS.

Background Optimising intranasal distribution and retention of topical therapy is essential for effectively managing patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). This study presents a new technique for quantifying in vitro experiments of fluticasone propionate deposition within the sinuses of a 3D-printed model from a post-FESS patient. Methods Circular filter papers were placed on the sinus surfaces of the model. Deposition of fluticasone on the filter paper was quantified using high-performance liquid chromatography (HPLC) assay-based techniques. The deposition patterns of two nasal drug delivery devices, an aqueous nasal spray (Flixonase) and metered dose inhaler (Flixotide), were compared. The effects of airflow (0 L/min vs. 12 L/min) and administration angle (30° vs. and 45°) were evaluated. Results Inhaled airflow made little difference to sinus deposition for either device. A 45° administration angle improved frontal sinus deposition with the nasal spray and both ethmoidal and sphenoidal deposition with the inhaler. The inhaler provided significantly better deposition within the ethmoid sinuses (8.5x) and within the maxillary sinuses (3.9x) compared with the nasal spray under the same conditions. Conclusion In the post-FESS model analysed, the inhaler produced better sinus deposition overall compared with the nasal spray. The techniques described can be used and adapted for in vitro performance testing of different drug formulations and intranasal devices under different experimental conditions. They can also help validate computational fluid dynamics modelling and in vivo studies.

BackgroundDespite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa influences their efficacy remains largely undefined.MethodsThirty subjects undergoing functional endoscopic sinus surgery (FESS) for bilateral CRS were randomized to one of three groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days) and 3) control (no antibiotics given). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal secretions, sinonasal tissues and serum at steady state. Nasal endoscopy (Modified Lund-Kennedy) and Gastrointestinal Symptom Rating Scale (GSRS) scores were recorded.ResultsAntibiotic concentrations in the nasal secretions were significantly lower compared to those in the serum and tissue (mean mucus/serum ratio at steady state = 0.16 and 0.37 for doxycycline and roxithromycin respectively; pp=0.04).ConclusionsAlthough the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complication of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS.

Background The aim of this study was to use computational fluid dynamics (CFD) to investigate the effects on nasal heat exchange and humidification of two different surgical techniques for reducing the inferior turbinate under different environmental conditions. Methods Virtual surgery using two techniques of turbinate reduction was performed in eight nasal airway obstruction patients. Bilateral nasal airway models for each patient were compared: 1) Pre-operative 2) Post inferior turbinoplasty 3) Post total inferior turbinate resection (ITR). Two representative healthy models were included. Three different environmental conditions were investigated 1) ambient air 2) cold, dry air 3) hot, humid air. CFD modelling of airflow and conditioning was performed under steady-state, laminar, inspiratory conditions. Findings Nasal conditioning is significantly altered following inferior turbinate reduction surgery, particularly with ITR under cold, dry inspired air (CDA). The degree of impairment is minor under the simulated range of environmental conditions (temperature = 12–40 °C; relative humidity = 13–80%). Streams of significantly colder air are found in the nasopharynx and more prevalent under CDA in ITR. These are related to high velocity flow streams, which remain cool in their centre throughout the widened inferior nasal cavity. Interpretation Reduced air-mucosal heat exchange and moisture carrying capacity occurs under cooler temperatures in patients following inferior turbinate surgery. The clinical impact in extremely cold and dry conditions in groups with poor baseline respiratory function, respiratory illness, or endurance athletes is of special interest.

ObjectivesMajor hepatic resection is now performed frequently and with relative safety, but is accompanied by significant pathophysiological changes. The aim of this review is to describe these changes along with interventions that may help reduce the risk for adverse outcomes after major hepatic resection.MethodsThe MEDLINE, EMBASE and CENTRAL databases were searched for relevant literature published from January 2000 to December 2011. Broad subject headings were ‘hepatectomy/’, ‘liver function/’, ‘liver failure/’ and ‘physiology/’.ResultsPredictable changes in blood biochemistry and coagulation occur following major hepatic resection and alterations from the expected path indicate a complicated course. Susceptibility to sepsis, functional renal impairment, and altered energy metabolism are important sequelae of post-resection liver failure.ConclusionsThe pathophysiology of post-resection liver failure is difficult to reverse and thus strategies aimed at prevention are key to reducing morbidity and mortality after liver surgery.