Chronic renal homograft function. Correlation with histology and lymphocyte antigen matching

Renal function was studied in twenty-nine of thirty-four surviving renal allograft recipients from an initial group of sixty-four patients two years after transplantation. Mean clearances of inulin and PAH were, respectively, greater than and equal to half the donors' initial predicted clearances. Minimum urine osmolality during water diuresis was greater, and maximum urine osmolality during hydropenia was less than normal, an effect attributable partly to enhanced solute load in a single transplanted kidney. Patients with compatible donor-recipient lymphocyte antigens demonstrated statistically better function than those with one or more incompatibilities, although there was a definite degree of overlap between the two groups. In contrast, little correlation could be demonstrated between the cumulative histopathology and renal clearances. Renal function in patients with compatible donors was statistically greater than half the donors' initial predicted function. Serial increase in renal clearances was documented in one patient with a compatible donor. Serial decreases were demonstrated in two patients with incompatible donors. These findings suggest that hypertrophy of the denervated, transplanted kidney occurs when immune reaction is minimal. © 1967

Use of Living Donors for Renal Homotransplantation

The procedure is described which is followed at the University of Colorado Medical Center for the selection and evaluation of living donors for renal homotransplantation. Priority is given to volunteers who have a close genetic relationship to the recipient. The aortogram is the single most useful test for determining which kidney to be used. If either organhas a single artery, it can be employed for homografting without fear of encountering anatomic difficulties at the time of its subsequent insertion into the recipient. Twenty-two left and 18 right kidneys have been excised. The donor operation has been a safe one. The only complications have been two pneumothoraces, one atelectasis, one transient peroneal nerve palsy, and two subcutaneous wound infections. Renal hyperplasia of the remaining kidney apparently occurs promptly since the creatinine clearance returns to or toward normal within a few weeks after operation. Interestingly, the same phenomenon is also observed in the homograft in those recipients who have a successful result. The steps in the donor operation are described for both right and left sides. Wide exposure, block removal of the specimen, and meticulous technique are required both to protect the donor from surgical accidents and to insure a homograft of high quality. Homograft cooling is provided eitherby total body hypothermia of the donor or by a method in which intra-arterial infusion of a chilled electrolyte solution isused. The relative future roles of living and cadaveric donors are discussed. The results with parental or sibling donations have been good enough to justify further employment of these sources. In cases in which a genetically unrelated donor must be used, a sounder policy may be to seek cadaveric organs, especially if the recipient falls in an older age group. © 1964 American Medical Association All rights reserved

Renal homografts in patients with major donor-recipient blood group incompatibilities

Three documented cases of clinical renal transplantation in which the donor and recipient patients had different major blood types have been presented. The relationship of the donor-recipient pairs ranged from that of sister-to-brother to that of totally unrelated patients of different races. The renal homografts were obtained from living donors in 2 cases and from a recently dead cadaver in the third. Renal function was prompt and excellent when living donors were used, and more indolent when a cadaver kidney subjected to a long period of ischemia was employed. Two of the patients have normal renal function after 74 and 49 days. The third patient died with rejection and sepsis 24 days after transplantation. This study demonstrates the feasibility of obtaining both immediate and prolonged renal function despite the presence of major blood group incompatibilities between donor and recipient patients. This knowledge should expand the donor pool, making it possible to transfer renal homografts under much less stringent requirements than has been the case in the past. © 1964

Arduous implementation: Does the Normalisation Process Model explain why it's so difficult to embed decision support technologies for patients in routine clinical practice

Background: decision support technologies (DSTs, also known as decision aids) help patients and professionals take part in collaborative decision-making processes. Trials have shown favorable impacts on patient knowledge, satisfaction, decisional conflict and confidence. However, they have not become routinely embedded in health care settings. Few studies have approached this issue using a theoretical framework. We explained problems of implementing DSTs using the Normalization Process Model, a conceptual model that focuses attention on how complex interventions become routinely embedded in practice.Methods: the Normalization Process Model was used as the basis of conceptual analysis of the outcomes of previous primary research and reviews. Using a virtual working environment we applied the model and its main concepts to examine: the 'workability' of DSTs in professional-patient interactions; how DSTs affect knowledge relations between their users; how DSTs impact on users' skills and performance; and the impact of DSTs on the allocation of organizational resources.Results: conceptual analysis using the Normalization Process Model provided insight on implementation problems for DSTs in routine settings. Current research focuses mainly on the interactional workability of these technologies, but factors related to divisions of labor and health care, and the organizational contexts in which DSTs are used, are poorly described and understood.Conclusion: the model successfully provided a framework for helping to identify factors that promote and inhibit the implementation of DSTs in healthcare and gave us insights into factors influencing the introduction of new technologies into contexts where negotiations are characterized by asymmetries of power and knowledge. Future research and development on the deployment of DSTs needs to take a more holistic approach and give emphasis to the structural conditions and social norms in which these technologies are enacte

The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>Many cystic fibrosis (CF) patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8) is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals.</p> <p>Methods</p> <p>Experiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects). Cells from the 2^ndto 5^thpassage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca²⁺]_i), cell contraction, migration and proliferation.</p> <p>Results</p> <p>The IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM) induced a peak Ca²⁺release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p < 0.05). IL-8 induced contraction was greater in CF cells compared to control. Furthermore, IL-8 exposure resulted in greater phosphorylation of myosin light chain (MLC₂₀) in CF than in control cells. In addition, MLC₂₀expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells.</p> <p>Conclusion</p> <p>ASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC₂₀. Higher expression of MLC₂₀by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.</p