Health status and quality of life following cardiac transplantation

There is little information regarding the functional status and quality of life of cardiac transplant patients. This investigation is the largest study describing outcome up to 10 years after cardiac transplantation. We conducted a cross-sectional survey of 200 cardiac transplant recipients using the Sickness Impact Profile and a supplementary questionnaire. The response rate was 48%. The median duration post-cardiac transplantation was 2.3 years (range, 0.5 to 9.7 years). The median age was 53 years (range, 27.1 to 68.7). In comparison to previously published studies, our sample of cardiac transplant recipients had worse quality of life than normals, similar scores to cardiac arrest survivors and post-myocardial infarction patients, and better quality of life than patients with low back pain. We found that those not working (44%) reported a lower quality of life. Musculoskeletal-neurologic complaints were highly prevalent, with generalized weakness in 54% responding, fatigue in 42%, and low back pain in 37%. Lower quality of life was found in patients reporting a higher number of musculoskeletal-neurological disorders. We conclude that there are specific areas for rehabilitation intervention in patients post-cardiac transplantation, and suggest areas for future research directed towards enhancing quality of life for cardiac transplant recipients.     

Seizure detection of newborn EEG using a model-based approach

Seizures are often the first sign of neurological disease or dysfunction in the newborn. However, their clinical manifestation is often subtle, which tends to hinder their diagnosis at the earliest possible time. This represents an undesirable situation since the failure to quickly and accurately diagnose seizure can lead to longer-term brain injury or even death. In this paper we consider the problem of automatic seizure detection in the neonate based on electroencephalogram (EEG) data. We propose a new approach based on a model for the generation of the EEG, which is derived from the histology and biophysics of a localized portion of the brain. We show that by using this approach, good detection performance of electrographic seizure is possible. The model for seizure is first presented along with an estimator for the model parameters. Then we present a seizure-detection scheme based on the model parameter estimates. This scheme is compared with the quadratic detection filter (QDF), and is shown to give superior performance over the latter. This is due to the ability of the model-based detector to account for the variability (nonstationarity) of the EEG by adjusting its parameters appropriately.     

Activation of protein kinase C delta by the c-Abl tyrosine kinase in response to ionizing radiation

The c-Abl protein tyrosine kinase is activated by ionizing radiation (IR) and certain other DNA-damaging agents. The present studies demonstrate that c-Abl associates constitutively with protein kinase C delta (PKCdelta). The results show that the SH3 domain of c-Abl interacts directly with PKCdelta. c-Abl phosphorylates and activates PKCdelta in vitro. We also show that IR treatment of cells is associated with c-Abl-dependent phosphorylation of PKCdelta and translocation of PKCdelta to the nucleus. These findings support a functional interaction between c-Abl and PKCdelta in the cellular response to genotoxic stress.     

Kinetics of DNA repair synthesis in guinea-pig pancreatic slices following in vitro exposure to N-methyl-N-nitrosourethane

In vitro exposure of guinea-pig pancreatic slices to NMUT resulted in an increase in hydroxyurea-insensitive 3H-TdR incorporation into DNA; this represents DNA repair synthesis following NMUT-induced DNA damage. The kinetics of this hydroxyurea-insensitive 3H-TdR incorporation suggest that the NMUT-induced DNA damage is largely repaired within 2 hours.     

Myocardial infarction as a complication of new interventional devices

Percutaneous transluminal coronary balloon angioplasty has been associated with acute myocardial infarction (MI) as a complication of the procedure. Abrupt closure, distal coronary embolization, intimal dissection, coronary spasm, and acute thrombosis are the principal etiologies. New interventional devices (stent, laser, and atherectomy catheters) have been introduced as alternatives or adjuncts to balloon angioplasty. With use of the New Approaches to Coronary Intervention Registry, the incidence, predictors, and outcome of MI as a complication of using these devices as the primary mode of intervention were studied. There were 3,265 patients from 39 participating centers in the cohort treated with new devices. MI was reported as an in-hospital complication of using new devices in 154 patients (4.7%), including Q-wave MI in 36 patients (1.1%), and non-Q-wave MI in 119 patients (3.6%). MI rates were not significantly different among all patients with devices in the cohort treated with atherectomy (directional, extractional, rotational), laser (AIS, Spectranetics) or the Palmaz-Schatz stent. Multivariate logistic regression showed that post-procedure MI was associated with multivessel disease, high surgical risk, postinfarction angina, and presence of a thrombus prior to the procedure. Prior percutaneous transluminal coronary angioplasty was inversely related to the incidence of MI. When a specific cause of MI could be detected, the main etiologies were: coronary embolus 16.9%, and abrupt closure 27.3%. Other major in-hospital complications were higher in the MI group than the non-MI group: death 7.8% versus 0.8% (p <0.001), and bypass surgery 13.6% versus 1.7% (p <0.001). At 1 year, mortality rates remain higher at 12.9% in the MI group versus 4.9% in the non-MI group (p <0.01). Despite different indications for the use of new devices, they were not predictors for MI with the exception of the rotablator. The incidence of MI (1.1% Q-wave, 3.6% non-Q-wave) was comparable to previously reported rates for balloon angioplasty. The occurrence of MI is associated with an increase in other in-hospital complications and a doubling of 1-year mortality.     

Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow

Eosinophils are known to express cytokines capable of promoting fibrosis. Interleukin-5 (IL-5) is important in regulating eosinophilopoiesis, eosinophil recruitment and activation. Lung IL-5 expression is elevated in pulmonary fibrosis, wherein the eosinophil is a primary source of fibrogenic cytokines. To determine the role of IL-5 in pulmonary fibrosis, the effects of anti-IL-5 antibody were investigated in a model of bleomycin-induced pulmonary fibrosis. Fibrosis was induced in mice by endotracheal bleomycin treatment. Animals were also treated with either anti-IL-5 antibody or control IgG. Lungs were then analyzed for fibrosis, eosinophil influx, chemotactic activity, and cytokine expression. The results show that a primary chemotactic activity at the height of eosinophil recruitment is IL-5. Furthermore, anti-IL-5 antibody caused significant reduction in lung eosinophilia, cytokine expression, and fibrosis. These findings taken together suggest an important role for IL-5 in pulmonary fibrosis via its ability to regulate eosinophilic inflammation, and thus eosinophil-dependent fibrogenic cytokine production.