Afhandling--Copenhagen. / Summary also in Danish. Bibliography: p. 253-258.

Abstract Genetic factors have been implicated to play a role in both degenerative lumbar spinal stenosis (LSS) and intervertebral disc disease (IDD). Sequence variations in the genes coding for collagen IX and inflammatory mediators have been indicated as risk factors for IDD. Nine genes coding for intervertebral disc (IVD) collagens I, II, IX and XI and aggrecan (AGC1) were analyzed for sequence variations in 29 Finnish individuals with LSS. In addition, two polymorphisms in the vitamin D receptor gene and one in the matrix metalloproteinase-3 gene were studied. Study subjects were analyzed both clinically and radiologically. Results indicated an association between the COL11A2 IVS6-4 a to t polymorphism and LSS (p = 0.0016). Moreover, the t/t genotype was found more often in the patient group compared to controls (p = 0.0011). A novel splicing mutation, likely resulting in the synthesis of a truncated protein, was identified in COL9A2. Eight hundred four Chinese individuals were screened for the presence of the Trp2 and Trp3 alleles. The Trp2 allele was found in 20% of the individuals compared to the previously reported 5% in Finnish patients with IDD characterized by sciatica. The Trp2 allele was found to predispose to IVD degeneration and end plate herniations, increasing the risk by 2.4-fold from 40 to 49 years of age. In addition, the degeneration was worse in individuals with the Trp2 allele. The risk for annular tears was 4-fold greater in study subjects from 30 to 39 years of age who were Trp2 positive. Surprisingly, the Trp3 allele was absent even though it was found in about 9% of Finnish individuals. One hundred fifty-five Finnish individuals with IDD characterized by sciatica were analyzed for sequence variations in four genes coding for inflammatory mediators IL1A, IL1B, IL6, and TNFA. In addition, sixteen polymorphisms in inflammatory mediator genes were analyzed. The results identified an association between sciatica and the E5+15T>A polymorphism in IL6 (p = 0.007). A significant association was also seen in the IL6 haplotype analysis (-597 g>a, -572 g>c, -174 g>c and E5+15T>A). The association of the GGGA haplotype with the disease was highly significant (p = 0.0033).

With supplement of 8 reprints .

Background and hypothesis: Valvar pulmonary stenosis is a common congenital heart defect. Progression of stenosis over time, even when mild initially, has been shown by serial cardiac catheterization studies in children and adults. We studied the natural history of asymptomatic valvar pulmonary stenosis diagnosed in infancy with two-dimensional echocardiography and Doppler method. Methods: Between November 1986 and March 1993, 51 infants in the Northeast Tennessee and Southwest Virginia region were clinically diagnosed to have isolated valvar pulmonary stenosis. In 40 patients, the diagnosis was confirmed by two-dimensional echocardiogram/Doppler and color- flow mapping study at the time of presentation, and only their course is reported. Of 40 infants, six asymptomatic infants (15%) showed rapid progression of pulmonary stenosis over a relatively short period of time. Within the first 6 months of life, three of the six infants showed worsening of the stenosis needing intervention (one had surgical vulvectomy and the others had percutaneous balloon valvuloplasty). The three other infants showed a more gradual increase of pulmonary stenosis over the first 2 years of life. Results: Pulmonary stenosis even when mild can worsen in infancy, and it is not possible to predict which patients will follow this course. In our group of asymptomatic infants with initial mild pulmonary stenosis, 15% developed significant stenosis that needed intervention. Conclusion: We recommend frequent follow-up of asymptomatic infants with mild pulmonary stenosis during the first 2 years of life to detect rapid progression that may need intervention.

We report our experience with asymptomatic valvar aortic stenosis diagnosed during infancy. During the period between November 1, 1986 and October 31, 1992 a total of 13 infants were diagnosed with asymptomatic aortic stenosis, 5 of whom showed rapid progression over the first 2 years of life. Two of these asymptomatic infants had severe aortic stenosis by 2 months of age, requiring intervention. We agree that aortic stenosis is a progressive lesion even in mild cases, but we emphasize the need for close clinical and echocardiographic follow-up of these asymptomatic children during infancy to prevent congestive heart failure and sudden death.

No description available.

Cardiovascular disease is responsible for the majority of morbidity and mortality in the United States. Physiologically healthy flow rarely displays turbulent behavior, thereby maintaining normal shear levels. The presence of vortical flow structures, however, alters the hemodynamical characteristics within the system, which has significant effect upon shear stress (SS) and wall shear stress (WSS) levels, as well as particle residence times. The relationship between these hemodynamic parameters and vascular injury response is of great relevance to understanding the cardiovascular disease process. In this work, new methods and algorithms are developed and presented for resolving, both globally and locally, the spatial and temporal variations of shear stress (SS) and WSS for in vitro models of the human cardiovascular system. Advancements in global measurements are based on improving the accuracy of SS and WSS estimation from time-resolved Digital Particle Image Velocimetry (DPIV) velocity measurements. A new velocity derivative method, the fourth-order noise-optimized compact-Richardson implicit scheme, has been developed, overcoming the obstacle of minimizing both the bias and random error in temporal/spatial derivative estimations. The resulting error is on the same order as the velocity measurement error for global measurements which results in an order of magnitude accuracy improvement. The method has been extended to WSS measurements, and combined with a new method of mirroring/reflecting a flow field over its boundary in order to achieve higher-order estimation. For moving boundaries an edge detection cross-correlation algorithm has been developed and characterized, yielding sub-pixel accuracy in measuring dynamic wall position prior to estimating WSS. An original microelectromechanical system (MEMS) WSS sensor capable of delivering high sensitivity, frequency response and accurate WSS measurements has been developed and characterized in this work. / Ph. D.

Objective - To determine if an endoscopic-assisted foraminotomy significantly increases the area of the L7-S1 intervertebral foramen and if, over a 12-week time period, there is stenosis of the treated foramen. Study Design - Prospective, experimental study Animal Population - Six, clinically normal adult dogs. Methods - Using endoscopic assistance a unilateral L7-S1 foraminotomy was performed. Computed tomography of the region was performed in the pre-operative, immediately post-operative and 12-week post-operative time periods. Parasagittal area measurements were obtained at the entry, middle and exit zones of the treatment and control foramen for each period. Objective and subjective data were compared among dogs, by time period and treatment status. Results - Endoscopic assisted foraminotomy resulted in a significant increase in the mean parasagittal foramen area (mPFA) of the entry and middle zones in the immediate post-operative period. The exit zone was not made significantly larger at any time period. The foramen remained significantly larger at the 12-week post-operative period in the middle zone only. However, some decrease in the surgically created foramen enlargement occurred at all three levels. The dogs tolerated the procedure well, but did have a mild, temporary delay of functional return post-operatively. Conclusions - Endoscopic assisted foraminotomy in the canine patient can be performed for certain regions of the foramen allowing enhanced visibility in the spinal canal during the procedure. The foramen can be surgically enlarged at the entry and middle zones using this technique. There is some reduction of the foraminal enlargement at 12-weeks post-operative. The clinical significance of this reduction is not evident from this study. Clinical Relevance - Endoscopic assisted foraminotomy could be used to improve intra-operative visualization in dogs with foraminal stenosis as a component of degenerative lumbosacral stenosis. / Master of Science

No description available.

Diss. Linköping : Linköpings universitet, 2008.