No description available.

No description available.

The purpose of this study was to determine the effect of reversible fetal tracheal occlusion on lung development. Nine fetal sheep were divided into two groups. Group 1 had intratracheal balloons placed and the balloons left inflated for 21-28 days. Group 2 consisted of littermates that served as controls. They had either uninflated balloons placed or were left unoperated. Tracheal pressure measurements were periodically recorded and the amniotic fluid pressure served as a reference. The animals were sacrificed near term and the lungs, heart and liver were weighed and corrected for body weight. Standard morphometry was used to compare the lungs further and the lung DNA and protein content were measured. Tracheal damage from the balloon catheter was also assessed. / Tracheal pressure was 3.85 ($ pm$.49 S.E.) mm Hg in experimental animals while it was an average of $-$0.27 ($ pm$.27 S.E.) mm Hg in controls (p $<$.0001). Tracheal occlusion increased lung weight and volume by 2-3 times (p $<$.0001 and p =.0006, respectively) while heart and liver weights remained similar to controls. Airspace fraction and radial alveolar counts were raised (p =.044 and p =.0002, respectively) and alveolar number per body weight was doubled (p $<$.0001). The alveolar number per lung volume was preserved, however, as was the DNA and protein content per unit weight of lung tissue. The chronic indwelling balloon catheter caused some mucosal and submucosal damage at the balloon site and proximal to it. / These results show that tracheal occlusion leads to an elevation of intratracheal pressure that is associated with a tremendous increase in lung growth over a short period in the third trimester fetal sheep. The techniques used in this experiment may be easily modified for use with endoscopic surgical equipment.

No description available.

The aim of this study was to examine apo(a)B particles distribution among plasma lipoproteins in two situations in which triglyceride-rich lipoproteins are increased: in normolipidemic subjects after a fat load and in patients with endogenous hypertriglyceridemia. / The results obtained demonstrate that, in hypertriglyceridemic patients, the distribution of apo(a)B particles among lipoprotein fractions is different than that observed in normotriglyceridemic subjects. These differences in distribution are a result of the association of apo(a)B particles with TG-rich lipoproteins. Contrary to apo(a)B particles found in the cholesterol-rich fraction apo(a)B particles in the TG-rich fraction are associated with lipoproteins of different sizes. The amount of apo(a)B particles in the TG-rich fraction could represent up to 50% of its total concentration and may contribute to the atherogenic and the thrombogenic potential of VLDL in HTG.

Body composition studies (BC) by a multiple isotope dilution technique were performed for studying nutritional parameters and nutritional support. A group of anthropometric, biochemical and immunological parameters were measured and the data indicated that these parameters were valid measures of the nutritional state for epidemiological studies; but, of little value in assessing the individual's nutritional state. Of 44 morbidly obese patients undergoing jejunoileal bypass, 33 patients lost only body fat. Eleven patients lost both body fat and body cell mass (BCM) thus developing protein malnutrition. Six of these malnourished patients had abnormal liver function tests (LFT), and both the BC and the LFT improved when calorie free amino acids were infused. BC studies were performed on TPN patients receiving one of four solutions. To evaluate the effect of these solutions on the daily repletion of the BCM a multiple linear regression was used. The regression indicated that the repletion of the depleted BCM was related to the lipid (p < .01) and carbohydrate (p < .001) infused, and the nutritional state (p < .001). Carbohydrate was more efficient than lipid, in repleting the BCM, and increasing protein above 1.26 gm/kg/day had no benefit.

Esophagogastroduodenal endoscopy (EGDE) is the most commonly performed endoscopic procedure in Canada and represents 51--65% of all gastrointestinal procedures performed in teaching hospitals. The routine use of conscious sedation during EGDE has facilitated its diffusion, ensured patient and physician satisfaction and has increased the potential risk of cardiorespiratory morbidity. It remains unclear if all adult ambulatory patients require routine conscious sedation prior to diagnostic EGDE, as the efficacy and safety of such a policy has not been rigorously studied in a North American population. / Patients were randomly assigned to sedation or placebo in a double-blind trial. / So far 360 patients of the anticipated patients have been enrolled, (182 randomized to sedation, 178 randomized to placebo). Groups were similar for all baseline characteristics. Eighty-one percent of patients randomized to placebo were able to complete EGDE without sedation. The major determinant of "successful endoscopy" was the use of sedation (OR = 7.52; 95% CI: 4.61--12.26). Preliminary subgroup analysis suggested that among patients greater than 55 yrs and with decreased pharyngeal sensitivity, there was a greater likelihood of successful unsedated endoscopy, when compared to other subsets (45% successful vs. 39% successful among the unstratified placebo population; 98% power). / The use of sedation does not improve technical adequacy. However, the use of sedation in the performance of EGDE is the strongest predictor of a successful endoscopy, patient self-reported satisfaction and willingness to repeat the procedure.

Obesity is an ever-growing problem of our society and, therefore, understanding the underlying endocrine causes is vital to both the prevention and treatment of this disease. This present thesis work was undertaken to better understand the impact of Acylation Stimulating Protein (ASP), an adipokine, on the physiology and pathophysiology of the adipose tissue. I have demonstrated, for the first time, that ASP participates in the recruitment of preadipocytes to become adipocytes (differentiation process). Although, the ASP effects were comparable to those of insulin, preliminary microarray analysis indicates that the early intracellular signaling pathways are likely quite different for both hormones. Furthermore, I have identified and begun to characterize an ASP receptor initially identified as C5L2. I have demonstrated that binding affinity of ASP and C3a (immediate ASP precursor) to C5L2 is similar to that observed in cells that are responsive to ASP (triglyceride synthesis stimulation, TGS). I have also shown, for the first time, that C5L2 is expressed in human adipose tissue, human skin fibroblasts and 3T3-L1 preadipocytes. Finally, the ASP signaling pathway resulting in increased TG synthesis has began to be explored using a "shot gun" approach. This initial phase of research has provided evidence of the involvement of phospholipase C and phosphoinositide 3-kinase in ASP signaling. Overall, the data presented in this thesis defines more clearly ASP-cell interaction and reveals potential targets for pharmacological agents that may prevent or slow down development of obesity in the future.

Human carcinoembryonic antigen (CEA), a well-known clinical tumor marker, belongs to the CEACAM family of cell surface intercellular adhesion molecules that represent a subset of the immunoglobulin superfamily. The glycophosphatidyl inositol-anchored family members, CEA and CEACAM6, are over-expressed in as many as 70% of all human cancers. This correlation suggested their role in tumor progression, which was supported by extensive results obtained with several systems in vitro and ex vivo. But their contribution and relevance in vivo remains uncertain without further validation. Since mice do not possess homologs of the CEA and CEACAM6 genes, transgenic mice harboring a 187 kb portion of the human CEACAM family gene locus contained in a bacterial artificial chromosome (CEABAC) that includes CEA, CEACAM3, CEACAM6, and CEACAM7 genes were constructed in this study. The spatiotemporal expression pattern of these genes is very similar to that in humans. The expression levels of these genes are gene dosage dependent. Moreover, these CEABAC mice are more susceptible to develop carcinogen-induced colon tumors and spontaneous lung tumors. At low to moderate expression levels of CEA/CEACAM6, a partial block in cell differentiation and a mild to moderate hyperproliferation were evident in the transgenic colon; however, these mice develop normally. At higher or tumor-like expression levels, a complete block in cell differentiation, an extreme hyperproliferation and an inhibition of apoptosis were observed. These mice showed reduced survival, growth retardation and chronic diarrhea, and showed massively enlarged colons comprising continuous non-focal cytological and architectural abnormalities, including a dysplastic and serrated adenomatous morphology, by only 3 months of age. These results suggested that, while moderate expression levels of CEA/CEACAM6 cause an imbalance of tissue homeostasis leading to increased tumor susceptibility, tumor-like exp

Multiple organ dysfunction is the most common cause of late mortality in trauma patients. Despite adequate resuscitation, hemorrhagic shock may progress to a state of profound systemic inflammation where the polymorphonuclear neutrophil (PMN) plays a key role. Resuscitation with hypertonic saline (HTS) may modulate the host inflammatory response in hemorrhagic shock. / A murine hemorrhagic shock model evaluated by cremaster intravital microscopy demonstrated significant in vivo attenuation of neutrophil rolling and adhesion to endothelium (EC) immediately after resuscitation with HTS, as compared to Ringer's lactate (RL). Concurrently, macromolecular leakage from the same post capillary venules was 45% lower in HTS animals. / To better simulate clinical conditions, the model was transformed to recreate two-hit conditions by subjecting resuscitated animals to a subsequent mimicked pulmonary infection. Attenuated neutrophil adhesion to endothelium in HTS animals persisted 5 and 22 hours after resuscitation. Additionally, compared to RL, HTS resuscitation reduced neutrophil lung sequestration (by the myeloperoxidase assay) and neutrophil lung transmigration (by histologic analysis) one day after resuscitation. HTS resuscitation also tended to improve cremaster and lung histologic injury a day after resuscitation conferring a 50% survival advantage for that time interval. / To determine if reductions in tissue injury were due to the ability of HTS to functionally block neutrophil adhesion to endothelium, another variation to the two-hit model was developed. Two additional groups were added to evaluate if supplementation of standard fluid resuscitation with anti adhesion monoclonal antibodies (anti-CD11b and anti-ICAM-1) would reproduce the effects of HTS alone. Although early EC/PMN interactions and 24-hour lung PMN accumulation were similarly attenuated by either HTS alone or RL with anti adhesion blockade, only HTS alone definitely reduced early in vivo macromolecule leakage, and one day lung histologic injury. / Hemorrhagic shock resuscitation with hypertonic saline reduces neutrophil activation and interactions with microvascular endothelium resulting in diminished lung PMN sequestration persisting well beyond the initial resuscitation phase. Yet the anti-adhesive effects of HTS are not essential for HTS-mediated reductions in tissue injury and organ dysfunction. Hypertonic resuscitation may prove to be an immunomodulatory therapy useful in critically ill trauma victims, the precise mechanisms of which need further elucidation.