Diseases of the chest, throat and nasal cavities ..

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Proton pump inhibitors and the risk of fractures in older adults: a population-based retrospective cohort study

Thesis (Master's)--University of Washington, 2016-06

Management of isolated orbital floor blow-out fractures: a survey of Australian and New Zealand oral and maxillofacial surgeons

Background: This is the first report of involvement of Australian and New Zealand oral and maxillofacial surgeons in the management of isolated orbital floor blow-out fractures and was conducted to obtain comparisons with the results from a recent similar survey of British oral and maxillofacial surgeons. Methods: A questionnaire survey was sent to all 113 practising members of the Australian and New Zealand Association of Oral and Maxillofacial Surgeons in April 2002 with a second mailout 1 month later. Results: Sixty-nine per cent of the respondents were referred isolated orbital floor blow-out fractures for manage-ment, and just over half of these respondents estimated that 50% or more of the cases went to surgery. The materials most commonly used in orbital floor reconstruction were resorbable membrane for small defects and autologous bone for large defects. Conclusion: As in Britain, management of isolated orbital floor blow-out fractures comprises part of the surgical spectrum for many oral and maxillofacial surgeons in Australia and New Zealand. The management protocol was observed to be very similar between the two groups.

Treatment of eight dogs with nasal tumours with a alternating doses of doxorubicin and carboplatin in conjunction with oral piroxicam

Objective To determine the efficacy and toxicity of chemotherapy in the treatment of canine nasal tumours. Design Retrospective clinical study Procedure Eight dogs with histologically confirmed nasal tumours were staged by means of complete blood count, serum biochemical analysis, cytological analysis of fine needle aspirate of the regional lymph nodes, thoracic radiographs and computed tomography scan of the nasal cavity. All dogs were treated with alternating doses of doxorubicin, carboplatin and oral piroxicam. All dogs were monitored for side effects of chemotherapy and evaluated for response to treatment by computed tomography scan of the nasal cavity after the first four treatments. Results Complete remission was achieved in four dogs, partial remission occurred in two dogs and two had stable disease on the basis of computed tomography evaluation. There was resolution of clinical signs after one to two doses of chemotherapy in all dogs. Conclusions This chemotherapy protocol was efficacious and well tolerated in this series of eight cases of canine nasal tumours.

Canine intra-nasal squamous cell carcinoma treated with chemotherapy prior to surgical resection

A 12-year-old male castrated Samoyed dog was presented with left-sided epistaxis and sneezing. Diagnostic procedures included haematology and biochemistry testing, thoracic radiography, fine needle aspiration of regional lymph nodes, CT, rhinoscopy, incisional biopsy and histopathology. Squamous cell carcinoma of the rostral nasal cavity was diagnosed, with no evidence of metastatic disease. External beam radiation was not an accessible treatment option. Complete surgical resection of the tumour would have required a larger, more disfiguring resection of nasal planum and maxilla than the owner was prepared to accept and may have been associated with an unacceptable morbidity. As an alternative, the extent of disease was reduced using a combination of carboplatin, doxorubicin and piroxicam chemotherapy. This allowed a less extensive nasal planum removal to be performed to remove residual disease with clean margins. The patient achieved a 14 month disease free interval from the time of surgery to the time of local recurrence. Survival time from diagnosis to eventual euthanasia for progressive local disease was 18 months.

Effect of cyclic pneumatic soft tissue compression on simulated distal radius fractures

We investigated the effect of pneumatic pressure applied to the proximal musculature of the sheep foreleg on load at the site of a transverse osteotomy of the distal radius. The distal radii of 10 fresh sheep foreleg specimens were osteotomized and a pressure sensor was inserted between the two bone fragments. An inflatable cuff, connected to a second pressure sensor, was positioned around the proximal forelimb musculature and the leg then was immobilized in a plaster cast. The inflatable cuff was inflated and deflated repeatedly to various pressures. Measurements of the cuff pressure and corresponding change in pressure at the osteotomy site were recorded. The results indicated that application of pneumatic pressure to the proximal foreleg musculature produced a corresponding increase in load at the osteotomy site. For the cuff pressures tested (109.8-238.4 mm Hg), there was a linear correlation with the load at the osteotomy site with a gradient of 12 mm Hg/N. It is conceivable, based on the results of this study, that a technique could be developed to provide dynamic loading to accelerate fracture healing in the upper limb of humans.

Health-protective behaviours and risk of fall-related hip fractures: a population-based case-control study

Background: fall-related hip fractures are one of the most common causes of disability and mortality in older age. The study aimed to quantify the relationship between lifestyle behaviours and the risk of fall-related hip fracture in community-dwelling older people. The purpose was to contribute evidence for the promotion of healthy ageing as a population-based intervention for falls injury prevention. Methods: a case-control study was conducted with 387 participants, with a case-control ratio of 1:2. Incident cases of fall-related hip fracture in people aged 65 and over were recruited from six hospital sites in Brisbane, Australia, in 2003-04. Community-based controls, matched by age, sex and postcode, were recruited via electoral roll sampling. A questionnaire designed to assess lifestyle risk factors, identified as determinants of healthy ageing, was administered at face-to-face interviews. Results: behavioural factors which had a significant independent protective effect on the risk of hip fracture included never smoking [adjusted odds ratio (AOR): 0.33 (0.12-0.88)], moderate alcohol consumption in mid- and older age [AOR: 0.49 (0.25-0.95)], not losing weight between mid- and older age [AOR: 0.36 (0.20-0.65)], playing sport in older age [AOR: 0.49 (0.29-0.83)] and practising a greater number of preventive medical care [AOR: 0.54 (0.32-0.94)] and self-health behaviours [AOR: 0.56 (0.33-0.94)]. Conclusion: with universal exposures, clear associations and modifiable behavioural factors, this study has contributed evidence to reduce the major public health burden of fall-related hip fractures using readily implemented population-based healthy ageing strategies.

Development of a novel in vitro system for nasal drug delivery development

There is currently, no ideal system for studying nasal drug delivery in vitro. The existing techniques such as the Ussing chamber and cell culture all have major disadvantages. Most importantly, none of the existing techniques accurately represent the interior of the nasal cavity, with its airflow and humidity; neither do they allow the investigation of solid dosage forms.The work in this thesis represents the development of an in vitro model system in which the interior characteristics of the nasal cavity are closely represented, and solid or minimal volume dosage forms can be investigated. The complete nasal chamber consists of two sections: a lower tissue, viability chamber and an upper nasal chamber. The lower tissue viability chamber has been shown, using existing tissue viability monitoring techniques, to maintain the viability of a number of epithelial tissues, including porcine and rabbit nasal tissue, and rat ileal and Payers' patch tissue. The complete chamber including the upper nasal chamber has been shown to provide tissue viability for porcine and rabbit nasal tissue above that available using the existing Ussing chamber techniques. Adaptation of the complete system, and the development of the necessary experimental protocols that allow aerosol particle-sizing, together with videography, has shown that the new factors investigated, humidity and airflow, have a measurable effect on the delivered dose from a typical nasal pump. Similarly, adaptation of the chamber to fit under a confocal microscope, and the development of the necessary protocols has shown the effect of surface and size on the penetration of microparticulate materials into nasal epithelial tissues. The system developed in this thesis has been shown to be flexible, in allowing the development of the confocal and particle-sizing systems. For future nasal drug delivery studies, the ability to measure such factors as the size of the delivered system in the nasal cavity, the depth of penetration of the formulation into the tissue are essential. Additionally, to have access to other data such as that obtained from drug transport in the same system, and to have the tissue available for histological examination represents a significant advance in the usefulness of such an in vitro technique for nasal delivery.

Biological barriers to the nasal delivery of peptide drugs

The nasal absorption of larger peptide and protein drugs is generally low. The importance of the mucus layer and enzymic degradation in reducing absorption were investigated. Reversed-phase high-performance liquid chromatographic (HPLC) methods were developed to assay a variety of compounds. Pig gastric mucus (PGM) was selected to investigate the importance of the mucus layer. A method of treating and storing PGM was developed and evaluated which was representative of the gel in vivo. The nature of the mucus barrier was evaluated in vitro with three-compartment diffusion cells and a series of compounds with differing physicochemical properties. Mucus retarded the diffusion of all the compounds with molecular weight and charge exerting a marked effect. Binding to mucus was investigated by a centrifugation method. All of the compounds tested were found to bind to mucus with the exception of the negatively charged molecule benzoic acid. The small peptides did not demonstrate greater binding to mucus than any of the other compounds evaluated. The effect of some absorption enhancers upon the rate of diffusion of tryptophan through mucus was determined in vi tro. At the concentrations employed the enhancers EDTA, N-acetylcysteine and taurodeoxycholic acid exerted no effect, whilst taurocholic acid and cholic acid, were found to slightly reduce the rate of diffusion. The intracellular and luminal proteolytic activity of the nose was investigated in the sheep animal model with a nasal mucosal homogenate and a nasal wash preparation respectively and a series of chemically similar peptides. Hydrolysis was also investigated with the proteolytic enzymes carboxypeptidase A, cytosolic leucine aminopeptidase and microsomal leucine aminopeptidase. Sheep nasal mucosa possesses significant peptide hydrolase activity capable of degrading all the substrates tested. Considerable variation in susceptibility was observed. Degradation occurred excl us i ve ly at the pept ide bond between the aromatic amino ac id and glycine, indicating some specificity for aromatic amino acids. Hydrolysis profiles indicated the presence of both aminopeptidase and carboxypeptidase enzymes. The specific activity of the microsomal fraction was found to be greater than the cytosolic fraction. Hydrolysis in the nasal wash indicated the presence of either luminal or loosely-bound proteases, which can degrade peptide substrates. The same specificity for aromatic amino acids was observed and aminopeptidase activity demonstrated. The specific activity of the nasal wash was smaller than that of the homogenate.

Physeal Growth Plate Fractures: Implications for the Pediatric Athlete

Pediatric musculoskeletal trauma accounts for most childhood injuries. The anatomy and physiology of the pediatric skeleton is unique as is its response to trauma. The pediatric skeleton has periods of rapid growth; therefore the effect of trauma to the musculoskeletal system may have significant long-term complications.