The effect of absorbable packing on the healing of nasal respiratory epthelium after endoscopic sinus surgery (ESS) was examined in a diseased sheep model. Full thickness injuries were created on the lateral nasal wall of sheep infested with Oestrus ovi. Sites of injury were packed on one side with hyaluronic acid (HA) packing or hyaluronic acid packing impregnated with insulin-like growth factor- 1 (HA+IGF1) in a randomized fashion. The opposite side was left unpacked as a control. Biopsies were obtained for light microscopy, scanning electron microscopy, and ciliary beat frequency (CBF) analysis over a period of 16 weeks. Statistical analysis of results was performed in order to determine if any intervention had any impact on healing and to determine if there was any correlation between extent of regeneration as assessed by electron microscopy and CBF. Furthermore assessment of the effect of isotonic and hypertonic saline on ciliary beat frequency was performed in healthy human volunteers. Reepithelialization was increased in the HA+IGF1 group compared to the HA group and controls at eight weeks after injury but not at later time points. Cilial regeneration was improved in the HA+IGF1 group compared to the HA group and controls at 16 weeks. CBF was noted to be worse at the eight week time point with the HA+IGF1 group compared to the HA group and controls, but no other statistically significant effects on CBF were noted. This most likely represents a spurious finding. Wide distributions of CBF results were noted, reflecting numerous missing data points due to methodological difficulties. There was a trend noted toward increased CBF with improved grades of reciliation, although this correlation was not statistically significant. However this trend was supported by the finding of statistically significant differences between individual and combined grades of reciliation. Hypertonic saline was found to have a ciliostimulatory effect when compared to normal saline at 5 minutes after administration in healthy human subjects. This effect had disappeared by 60 minutes after administration. It is suggested that the presence of insulin-like growth factor- 1 at the time of mucosal injury improves epithelial regeneration in the short term, but is not sufficient for this effect to be sustained. This improved early epithelial regeneration forms a foundation for cilial regeneration, as is reflected in an improved grade of reciliation at 16 weeks. Our interventions had no effect on CBF, and various experimental problems made it difficult to provide further comment on CBF results. There is evidence that CBF improves as the grade of cilial regeneration improves following ESS. Furthermore, hypertonic saline appears to also have a positive impact on CBF, which is likely to reflect changes in the rheological properties of mucous. A number of possible avenues of enquiry are delineated and recommendations for future research are outlined. / Thesis (M.S.)--Department of Surgery, 2005.

The effect of absorbable packing on the healing of nasal respiratory epthelium after endoscopic sinus surgery (ESS) was examined in a diseased sheep model. Full thickness injuries were created on the lateral nasal wall of sheep infested with Oestrus ovi. Sites of injury were packed on one side with hyaluronic acid (HA) packing or hyaluronic acid packing impregnated with insulin-like growth factor- 1 (HA+IGF1) in a randomized fashion. The opposite side was left unpacked as a control. Biopsies were obtained for light microscopy, scanning electron microscopy, and ciliary beat frequency (CBF) analysis over a period of 16 weeks. Statistical analysis of results was performed in order to determine if any intervention had any impact on healing and to determine if there was any correlation between extent of regeneration as assessed by electron microscopy and CBF. Furthermore assessment of the effect of isotonic and hypertonic saline on ciliary beat frequency was performed in healthy human volunteers. Reepithelialization was increased in the HA+IGF1 group compared to the HA group and controls at eight weeks after injury but not at later time points. Cilial regeneration was improved in the HA+IGF1 group compared to the HA group and controls at 16 weeks. CBF was noted to be worse at the eight week time point with the HA+IGF1 group compared to the HA group and controls, but no other statistically significant effects on CBF were noted. This most likely represents a spurious finding. Wide distributions of CBF results were noted, reflecting numerous missing data points due to methodological difficulties. There was a trend noted toward increased CBF with improved grades of reciliation, although this correlation was not statistically significant. However this trend was supported by the finding of statistically significant differences between individual and combined grades of reciliation. Hypertonic saline was found to have a ciliostimulatory effect when compared to normal saline at 5 minutes after administration in healthy human subjects. This effect had disappeared by 60 minutes after administration. It is suggested that the presence of insulin-like growth factor- 1 at the time of mucosal injury improves epithelial regeneration in the short term, but is not sufficient for this effect to be sustained. This improved early epithelial regeneration forms a foundation for cilial regeneration, as is reflected in an improved grade of reciliation at 16 weeks. Our interventions had no effect on CBF, and various experimental problems made it difficult to provide further comment on CBF results. There is evidence that CBF improves as the grade of cilial regeneration improves following ESS. Furthermore, hypertonic saline appears to also have a positive impact on CBF, which is likely to reflect changes in the rheological properties of mucous. A number of possible avenues of enquiry are delineated and recommendations for future research are outlined. / Thesis (M.S.)--Department of Surgery, 2005.

Preterm birth (PTB), defined as birth before 37 weeks of gestation, is the leading cause of neonatal morbidity, and survivors can face lifelong medical difficulties. PTB remains a clinical challenge worldwide, with rates of PTB rising in all countries with reliable data. A lack in understanding of the mechanisms that lead to PTB has made developing diagnostics and therapeutics challenging, and existing ones are often ineffective. For a successful pregnancy, the major reproductive organs and surrounding tissues must sustain the growing loads of pregnancy. The cervix is one of these major reproductive organs. The cervix sits at the base of the uterus and has a versatile mechanical function in pregnancy. First, it must stay closed during gestation while the fetus develops; second, the cervix must remodel sufficiently and timely to dilate and allow delivery. The proper timing and extent of remodeling are critical for a healthy pregnancy. Improper cervical remodeling is a final common pathway to PTB and is the tissue of focus in this thesis. To improve our ability to identify when a PTB birth will occur and ultimately be able to treat those at risk, this thesis will identify the mechanical role of three extracellular matrix (ECM) components at various gestational ages and evaluate the ability of two major hormones to alter cervix function. Using experimental techniques (large-deformation tensile testing, digital-image correlation, imaging, biochemical) and theoretical and computational techniques (constitutive modeling, finite element analysis), the mechanical behavior of whole mouse cervices will be characterized in wild type, genetic knockout, and hormone-treated animals. First, the loss of both Class-I small leucine rich proteoglycans (SLRPs), decorin and biglycan, is detrimental to cervix function in late gestation. When the cervix should be most compliant and extensible, cervices without decorin and biglycan cannot stretch and are as stiff as the nonpregnant cervix. The loss of these proteoglycans also slows the cervix’s stress dissipation mechanism in late gestation, which could put the cervix at increased risk for damage. The mechanism of stiffening and lost viscoelasticity indicates the fibril crosslinking associated with SLRPs is a structural mechanism of the ECM contributing to cervical remodeling. Second, the loss of hyaluronic acid diminishes the cervix’s mechanical function at every gestational age tested. For nonpregnant to mid-gestational age, the cervix is softer than normal. Though by late gestation, the loss of hyaluronic acid stiffens the cervix; this is at a point when the cervix should be at its softest. The loss of hyaluronic acid also decreases the cervix’s protective stress dissipation mechanism in late gestation. There is limited knowledge of the interaction of collagen, elastic fibers, and hyaluronic acid in the cervix. The significant mechanical role of hyaluronic acid in the cervix warrants exploration of the structural mechanisms of these functional changes. Third, the loss of endogenous hormones stiffens the tissue and increases extensibility compared to the nonpregnant cervix. The administration of estrogen recovers large amounts of extensibility (beyond the stretch level of a late gestation cervix), stiffens the tissue (such that it is stiffer than a nonpregnant cervix), and recovers a significant amount of cervix strength. Fourth, relaxin increases cervix extensibility in mid-gestation and endows the cervix with viscoelastic ability in late gestation. Altogether, understanding the correlation between these extracellular matrix components, hormones, and functional changes of the cervix is fundamental to teasing out mechanisms of cervical remodeling and developing improved PTB diagnostics and therapeutics.