Does primary brachial plexus surgery alter palliative tendon transfer surgery outcomes in children with obstetric paralysis?

<p>Abstract</p> <p>Background</p> <p>The surgical management of obstetrical brachial plexus palsy can generally be divided into two groups; early reconstructions in which the plexus or affected nerves are addressed and late or palliative reconstructions in which the residual deformities are addressed. Tendon transfers are the mainstay of palliative surgery. Occasionally, surgeons are required to utilise already denervated and subsequently reinnervated muscles as motors. This study aimed to compare the outcomes of tendon transfers for residual shoulder dysfunction in patients who had undergone early nerve surgery to the outcomes in patients who had not.</p> <p>Methods</p> <p>A total of 91 patients with obstetric paralysis-related shoulder abduction and external rotation deficits who underwent a modified Hoffer transfer of the latissimus dorsi/teres major to the greater tubercle of the humerus tendon between 2002 and 2009 were retrospectively analysed. The patients who had undergone neural surgery during infancy were compared to those who had not in terms of their preoperative and postoperative shoulder abduction and external rotation active ranges of motion.</p> <p>Results</p> <p>In the early surgery groups, only the postoperative external rotation angles showed statistically significant differences (25 degrees and 75 degrees for total and upper type palsies, respectively). Within the palliative surgery-only groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles. The significant differences between the early surgery groups and the palliative surgery groups with total palsy during the preoperative period diminished postoperatively (p < 0.05 and p > 0.05, respectively) for abduction but not for external rotation. Within the upper type palsy groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles.</p> <p>Conclusions</p> <p>In this study, it was found that in patients with total paralysis, satisfactory shoulder abduction values can be achieved with tendon transfers regardless of a previous history of neural surgery even if the preoperative values differ.</p

Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sjögren's syndrome

BACKGROUND: the classification criteria for primary Sjögren's syndrome (pSS) include a number of oral components. In this study we evaluated if salivary flow and composition as well as dental caries are oral markers of disease severity in pSS. METHODS: in 20 patients fulfilling the American-European Consensus criteria for pSS and 20 age-matched healthy controls whole and parotid saliva flow rates and composition, measures of oral dryness, scores of decayed, missing and filled tooth surfaces (DMFS), periodontal indices, oral hygiene, and dietary habits were examined. RESULTS: in pSS, salivary flow rates, pH, and buffer capacities were lower, and DMFS, salivary sodium and chloride concentrations higher than in the healthy controls. DMFS also correlated inversely to salivary flow rates and positively to oral dryness. Apart from slightly increased gingival index, and more frequent dental visits in pSS, the periodontal condition, oral hygiene or sugar intake did not differ between these two groups. In pSS, findings were correlated to labial salivary gland focus score (FS) and presence of serum-autoantibodies to SSA/SSB (AB). The patients having both presence of AB and the highest FS (>2) also had the highest salivary sodium and chloride concentrations, the lowest salivary phosphate concentrations, lowest salivary flow rates, and highest DMFS compared to those with normal salivary concentrations of sodium and chloride at a given flow rate. CONCLUSION: the salivary changes observed in some pSS patients reflect impaired ductal salt reabsorption, but unaffected acinar transport mechanisms, despite low salivary secretion. Our results suggest that changes in salivary flow and composition as well as dental caries may serve as potential markers of the extent of autoimmune-mediated salivary gland dysfunction in pSS. The study also indicates that the ductal epithelium is functionally affected in some pSS patients, which calls for future pathophysiological studies on the mechanisms underlying this impaired salt reabsorption

Subsets of intestinal dendritic cells and their role in orally-induced immune responses

Vaccination is the most effective means of preventing infectious diseases and improving global health. However, few vaccines have successfully been developed for protection at mucosal surfaces where most infectious pathogens enter our body. One major reason for this is the lack of adjuvants, immune enhancing agents, that can be administered together with the vaccine. The enterotoxin cholera toxin (CT) is a potent mucosal adjuvant but the toxicity precludes its use in humans. Derivatives of enterotoxins with reduced toxicity are today the most promising candidates for safe and efficient oral adjuvants. However, the underlying mechanisms for the adjuvant activity of enterotoxins are still not fully known. Dendritic cells (DCs) are immune cells that sense the microenvironment and confer T cells with ability to help B cells differentiate into antibody-producing plasma cells, necessary for vaccine-induced protection. Intestinal DCs are important both for immunity and tolerance. However, intestinal DCs constitute a heterogeneous population of cells. The function of intestinal DC subsets therefore needs to be defined further to understand how these contribute to tolerance under steady state and to induce immunity during infection or following oral immunization. In this thesis the role of intestinal DC subsets, in the induction of immune responses following oral administration of antigen, with or without CT as adjuvant, was elucidated. This was done after developing a microsurgical technique in mice that by cannulation of lymphatic vessels allows the direct collection of DCs that exit the intestine under steady state and following vaccination. This technique was combined with the use of genetically modified mice 1) in which DCs can be ablated; 2) that lack specific DC subsets; 3) that are deficient in intracellular signaling pathways in DCs or in other immune cells or 4) that lack CD47, a surface receptor known to influence cell migration. In the thesis we demonstrate the requirement of cDCs for the activation of antigen-specific T cells and the generation of antigen-specific antibodies following oral immunization when using limiting doses of antigen and CT as an adjuvant. In addition, we show in vivo that intact signaling through Gsα specifically in cDCs is essential for the oral adjuvant activity of CT. Using the cannulation technique we show that four subsets of DCs migrate from the intestine under steady state and following oral immunization. Selectively the CD11b-CD8+ subset does not show signs of activation after oral CT and this subset was also found to be dispensable for the generation of antigen-specific intestinal antibodies using this adjuvant. The necessity for CD11b+CD8- cDCs could not be establish in CD47 deficient mice, although these mice display significant reduction of this subset in intestinal tissues. Rather, expression of CD47 by non-hematopoietic cells is pivotal for intestinal antibody generation after oral immunization. Finally, signaling pathways involved in CT’s adjuvanticity were addressed and shown to be independent of classical TLR-signaling. Moreover, caspase 1/11 activity was not necessary for the generation of antigen-specific serum IgG but for intestinal IgA following oral immunization with CT. In conclusion, we have shown a requirement for cDCs and an intact signaling specifically in these cells for the oral adjuvant activity of CT. Furthermore we have identified that the generation of intestinal and systemic antibodies following oral immunization with CT are differentially regulated. These results may therefore have important implications for the development of improved oral vaccines