Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.

Community-associated methicillin-resistant Staphylococcus aureus transmission in households of infected cases: a pooled analysis of primary data from three studies across international settings.

Diverse strain types of methicillin-resistant Staphylococcus aureus (MRSA) cause infections in community settings worldwide. To examine heterogeneity of spread within households and to identify common risk factors for household transmission across settings, primary data from studies conducted in New York (USA), Breda (The Netherlands), and Melbourne (Australia) were pooled. Following MRSA infection of the index patient, household members completed questionnaires and provided nasal swabs. Swabs positive for S. aureus were genotyped by spa sequencing. Poisson regression with robust error variance was used to estimate prevalence odds ratios for transmission of the clinical isolate to non-index household members. Great diversity of strain types existed across studies. Despite differences between studies, the index patient being colonized with the clinical isolate at the home visit (P < 0·01) and the percent of household members aged <18 years (P < 0·01) were independently associated with transmission. Targeted decolonization strategies could be used across geographical settings to limit household MRSA transmission.

Molecular characterization of Staphylococcus aureus from outpatients in the Caribbean reveals the presence of pandemic clones.

Staphylococcus aureus infections continue to pose a global public health problem. Frequently, this epidemic is driven by the successful spread of single S. aureus clones within a geographic region, but international travel has been recognized as a potential risk factor for S. aureus infections. To study the molecular epidemiology of S. aureus infections in the Caribbean, a major international tourist destination, we collected methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates from community-onset infections in the Dominican Republic (n = 112) and Martinique (n = 143). Isolates were characterized by a combination of pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing (MLST) typing. In Martinique, MRSA infections (n = 56) were mainly caused by t304-ST8 strains (n = 44), whereas MSSA isolates were derived from genetically diverse backgrounds. Among MRSA strains (n = 22) from the Dominican Republic, ST5, ST30, and ST72 predominated, while ST30 t665-PVL+ (30/90) accounted for a substantial number of MSSA infections. Despite epidemiological differences in sample collections from both countries, a considerable number of MSSA infections (~10%) were caused by ST5 and ST398 isolates at each site. Further phylogenetic analysis suggests the presence of lineages shared by the two countries, followed by recent genetic diversification unique to each site. Our findings also imply the frequent import and exchange of international S. aureus strains in the Caribbean.

Hypercalcemia and pneumocystis Pneumonia after kidney transplantation: report of an exceptional case and literature review.

Pneumocystis jirovecii remains an important pathogen in solid organ transplant recipients. Although the overall incidence may be decreasing, after the adoption of effective prophylactic measures, the risk has not been abolished, and pneumocystis pneumonia (PCP) can be observed even many years after successful transplantation. Hypercalcemia develops frequently after renal transplantation and is commonly associated with preexisting secondary hyperparathyroidism. But the pathogenesis of hypercalcemia occurring later in the course of transplantation may be different, and other disease states, such as malignancy and opportunistic infections, must be considered. Hypercalcemia in conjunction with PCP is being increasingly reported in renal transplant patients. In all the cases, respiratory symptoms were prominent, hypercalcemia was of mild-to-moderate severity, parathyroid hormone concentration was decreased, and 1,25(OH)(2) D levels were extraordinarily or inappropriately high. We report the first case to our knowledge of severe hypercalcemia accompanying PCP, in a patient with previous total parathyroidectomy.

[Hyponatremia-workflow for intensive care physicians]. / Hyponatriämie ­ Workflow für Intensivmediziner.

Hyponatremia (sodium <135 mmol/l) is the most common electrolyte disorder. Despite identical serum concentrations, clinical symptomatology can vary greatly from mild to life-threatening. Accordingly, individual patients require immediate active treatment, while the majority of (mostly oligosymptomatic) patients should first undergo differentiated diagnosis. The most important element is the assessment of the clinical situation of the patient and never isolated laboratory chemical constellations: "Treat the patient, not the numbers".

Intentional ABO-incompatible lung transplantation.

We report on a case of intentional blood group incompatible lung transplantation. A blood group O cystic fibrosis patient was mechanically ventilated and put on interventional lung assist for severe respiratory decompensation. Since timely allocation of a blood group O donor lung was impossible, an AB deceased donor lung rescue allocation was accepted and the transplant performed using a pre-, peri- and postoperative antibody depletion protocol including plasmapheresis, ivIg administration, rituximab and immunoadsorption. Nine months after the transplant the patient is at home and well.

Do innocent victims threaten the belief in a just world? Evidence from a modified Stroop task.

Two experiments tested whether innocent victims threaten observers' belief in a just world. In both experiments, participants viewed an innocent victim then performed a modified Stroop task in which they identified the color of several words presented for brief exposures (followed by a mask) on a computer screen. When the threat to justice beliefs was presumably highest, color-identification latencies were greater for justice-related words than for neutral words. In Experiment 2, under conditions of high threat, justice-related interference predicted participants' tendency to disassociate themselves from and derogate the victim. These findings suggest that innocent victims do threaten justice beliefs and responses to these victims may, at times, be attempts to reduce this threat. The methodology presented here may be applied to future investigations of defensive, counternormative processes reflecting people's concern with justice.

Phasic changes in upper airway impedance.

To identify within breath variations in the mechanical properties of the isolated upper airway, we examined changes in impedance spectra over the course of the respiratory cycle. Changes were evaluated with a modified forced oscillation technique applied to the isolated, sealed upper airways of nine anesthetized mongrel dogs. Upper airway impedance spectra were studied during sequential 350 msec epochs. We found spectral changes which were reproducible within the respiratory cycle. Impedance spectra revealed that during mid-inspiration at the point of peak upper airway muscle activity, the low frequency real part decreased and the imaginary part was less negative and less steep. During late inspiration and early expiration the impedance values returned to their end-expiratory values. The only significant change in parameter estimates from a three-parameter model indicated an increase in compliance. Since these changes correlated not only with tidal flow through the lower trachea and lung but also with upper airway muscle activation, we reasoned that changes in impedance could have resulted from an increase in upper airway size. Therefore, we used a sealed speaker system and, while the animal was apnoeic, evaluated impedance at two different airway pressures and the resultant volumes. The changes in impedance spectra with a volume increase were similar to those seen during spontaneous breathing efforts. We conclude that the mechanical properties of the upper airway change during the respiratory cycle and that these changes correlate with the respiratory activation of upper airway muscles. We suspect that these changes in input impedance could reflect a change in the size of the airway rather than a true increase in elasticity.

The dimensionality of Type A behavior within a stressful work simulation.

The present study was conducted to examine the dimensionality of overt Type A behaviors elicited in a simulated stressful work environment. University students played a managerial role while being subjected to time and work-load pressures, and completed the Survey of Work Styles (SWS; Jackson & Gray, 1989). Eighteen behaviors, coded by two raters based on audiovisual recordings, yielded relatively high interrater reliabilities. Principal components analysis revealed four primary factors: Hurriedness, Irritability, Tension of the Lower Extremities, and Restlessness. These factors contribute to an understanding of Type A behavior in that they are the first to be derived from a purely observational approach rather than a combination of observational and self-report methods. Consistent with previous research, differential correlations between the factors and the SWS subscales supported a multi-dimensional interpretation of the Type A behavior pattern. Present findings are compared to those of previous studies of Type A dimensionality.