The impact of left ventricular dysfunction on cardiac donor transplant rates.

BACKGROUND: Because of the shortage of heart donors in the United States, efforts are necessary to maximize the yield of donor screening. The purpose of this study was to quantify the effects of left ventricular (LV) systolic dysfunction on heart donor use. METHODS: Using the California Transplant Donor Network database, the records of all potential organ donors screened between January 1997 and June 1998 were reviewed. After excluding subjects for whom family consent could not be obtained and subjects <13 or >or=60 years old, a study group of 223 potential heart donors was analyzed. The number of hearts not used because of LV dysfunction, coronary artery disease (CAD), valvular disease, and LV hypertrophy were quantified. A logistic regression model was developed to quantify the independent effect of LV dysfunction on donor use rates after adjustment for age, weight, and cause of death. RESULTS: Ninety-nine (44%) of the 223 potential donor hearts were not transplanted. Thirty-six of these hearts were not transplanted because of cardiac causes, primarily LV dysfunction (26 cases) and CAD (8 cases). The multivariable analysis showed that after adjusting for other donor variables, ejection fraction was the most significant predictor of non-use, with an odds ratio of 1.48 per 5-point decrease in ejection fraction. CONCLUSIONS: Left ventricular dysfunction is an important cause of failure to transplant adult donor hearts. Efforts to improve the yield of heart donor screening should focus on prevention or reversal of LV dysfunction.     

Downregulation of membrane type-matrix metalloproteinases in the inflamed or injured central nervous system

Background  

Matrix metalloproteinases (MMPs) are thought to mediate cellular infiltration in central nervous system (CNS) inflammation by cleaving extracellular matrix proteins associated with the blood-brain barrier. The family of MMPs includes 23 proteinases, including six membrane type-MMPs (MT-MMPs). Leukocyte infiltration is an integral part of the pathogenesis of autoimmune inflammation in the CNS, as occurs in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE), as well as in the response to brain trauma and injury. We have previously shown that gene expression of the majority of MMPs was upregulated in the spinal cord of SJL mice with severe EAE induced by adoptive transfer of myelin basic protein-reactive T cells, whereas four of the six MT-MMPs (MMP-15, 16, 17 and 24) were downregulated. The two remaining MT-MMPs (MMP-14 and 25) were upregulated in whole tissue.     

Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice

Background  

Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1β is primarily neurotoxic in ischemic stroke, TNF-α may have neurotoxic and/or neuroprotective effects. We investigated whether IL-1β and TNF-α are synthesized by overlapping or segregated populations of cells after ischemic stroke in mice.     

Nutritional immunomodulation leads to enhanced allograft survival in combination with cyclosporine A and rapamycin, but not FK506

BACKGROUND: Recently, specific immunonutrients were found to increase experimental allograft survival when combined with cyclosporine A (CsA). This study compared the effect on rat cardiac allograft survival when nutritional immunomodulation was used with CsA, rapamycin (Rapa), or tacrolimus (FK506). METHODS: Intra-abdominal ACI to Lewis cardiac allografts were performed and assessed daily by palpation. Study groups included untreated controls and those receiving CsA, Rapa, or FK506. Rats were fed ad libitum with Impact diet (fortified with fish oil, arginine, and RNA) or standard rat food. Further study groups were transplanted that received a donor-specific transfusion in addition to immunosuppression and diet. RESULTS: Allograft survival was extended by combining Impact with CsA (45.3+/-19 days) and Rapa (165.3+/-52 days), but not FK506 (12.4+/-3.2 days). Mean graft survival in the Rapa/Impact group met criteria for functional tolerance. The addition of a donor-specific transfusion did not lead to graft survival advantages over similar groups not receiving a donor-specific transfusion. CONCLUSIONS: The use of immunonutrients improves transplant outcome in animals treated with short courses of CsA and Rapa, but not FK506. These findings highlight the potential differences in the effects of nutritional immunomodulation with different immunosuppressive drugs in the treatment of transplant patients.     

Neuronal apoptosis after CNS injury: the roles of glutamate and calcium

While a role has been well established for excitotoxic necrosis in the pathogenesis of traumatic or ischemic damage to the CNS, accumulating evidence now suggests that apoptosis may also be a prominent contributor. In this review we focus on the role of glutamate and attendant intracellular calcium influx in triggering or modifying excitotoxic necrosis and apoptosis, raising the possibility that calcium influx may affect these two death pathways in opposite directions. Incorporating consideration of both pathways will probably be needed to develop the most effective neuroprotective treatments for CNS injury.     

Definition of the catalytic site of cytochrome c oxidase: specific ligands of heme a and the heme a3-CuB center.

The three-subunit aa3-type cytochrome c oxidase (EC 1.9.3.1) of Rhodobacter sphaeroides is structurally and functionally homologous to the more complex mitochondrial oxidase. The largest subunit, subunit I, is highly conserved and predicted to contain 12 transmembrane segments that provide all the ligands for three of the four metal centers: heme a, heme a3, and CuB. A variety of spectroscopic techniques identify these ligands as histidines. We have used site-directed mutagenesis to change all the conserved histidines within subunit I of cytochrome c oxidase from Rb. sphaeroides. Analysis of the membrane-bound and purified mutant proteins by optical absorption and resonance Raman spectroscopy indicates that His-102 and His-421 are the ligands of heme a, while His-284, His-333, His-334, and His-419 ligate the heme a3-CuB center. To satisfy this ligation assignment, helices II, VI, VII, and X, which contain these histidine residues, must be in close proximity. These data provide empirical evidence regarding the three-dimensional protein structure at the catalytic core of cytochrome c oxidase.     

Effects of personalised cue form on the learning of subordinate category names by aphasic and non-brain-damaged subjects

Background. Personalised cueing is a training method designed to facilitate naming of unknown, realistic visual stimuli (dog breed names). Creation of a personalised cue is similar to the use of mnemonic devices by normal individuals to remember important bits of information. Theoretical support for the method comes from Craik and Lockhart's depth-of-processing model of memory (1972). Several studies have shown that training with personalised cueing methods results in significantly higher levels of long-term naming accuracy than when subjects are trained with phonological cueing techniques. However, it has also been observed that all individuals are not equally proficient in creating personalised cues and that the nature of the information in personalised cues varies markedly from individual to individual. Aims. The objective of this study was to determine if the type of information contained in a personalised cue (cue form) affects the degree to which these cues facilitate learning of subordinate category names (dogs). Methods & Procedures. 600 personalised cues developed by 15 non-brain-damaged (NBD) and 15 aphasic individuals to learn the names of unknown dog breeds (e.g., Maltese) were examined. The cues were classified as one of five cue forms by three judges on two separate occasions approximately 1 month apart. Examination of intra-judge agreements for the cue forms yielded a total of 251 cues for analysis of cue form effects (127 aphasic; 124 non-brain-damaged). Outcomes and Results. To examine the effects of cue form on facilitation of naming, weighted recall scores were calculated for each cue based on accurate naming on probes one week, one month, and 6 months after training. Kruskal-Wallis analysis of variance by ranks (KWANOVA) was used to determine the effects of cue form on learning of the subordinate category names. Significant cue forms effects were found for aphasic but not non-brain-damaged participant cues. Mann-Whitney post-hoc comparisons of aphasic cues revealed that cues containing semantic information had significantly higher mean rankings than those containing phonological information and those containing a combination of phonological and semantic information. Conclusions. Two implications arise from the study with respect to the use of personalised cueing as a clinical procedure. One is that it may be necessary to exert some limited control over the creative process of developing a personalised cue to ensure the inclusion of semantic information in the cue itself. A second is that individuals who have problems accessing semantic information may require some training before attempting to create personalised cues. In such instances, it would be important to obtain information about the source of the individual's anomic deficits through careful testing before embarking on a training programme featuring personalised cueing.     

Privately insured medical patients are more likely to have a head CT

Previous studies suggest overuse disparity of head computed tomography (CT) in white pediatric trauma patients with minor head injuries. Our study is meant to determine if race or insurance status impacts the probability of obtaining head CT in patients with a Glasgow Coma Scale (GCS)?=?15. Using the 2008–2010 National Hospital Ambulatory Medical Care Survey for Emergency Departments (NHAMCS) database, the following variables were analyzed: race, emergency medical services (EMS) arrival, triage category, admission status, gender, age, and insurance status. Patients with injuries were excluded. All patients included had GCS?=?15. In univariate analysis, head CT is more likely to be obtained for patients in the following categories: Medicare insured, private insurance, Medicaid insured, and self-pay, EMS arrival, triage category immediate, and age >75 years. In logistic regression, race (white vs. black) was no longer significant, but there was disparity based on insurance status with privately insured patients more likely to receive a head CT (OR?=?1.683, 95 % CI?=?1.255–2.259). After controlling for the above inclusion variables and focusing on patients less likely to need CT (non-traumatic with GCS?=?15), privately insured patients were more likely to receive a head CT compared with uninsured. Race alone was not associated with an increased probability of receiving a head CT.