Report of a National Conference on Donation after Cardiac Death

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.     

ADP plays a key role in thrombogenesis in rats

The relative importance of ADP, arachidonic acid metabolites and serotonin as thrombogenic factors was evaluated in rats by comparing, after oral administration, the effects of two inhibitors of ADP-induced platelet aggregation (ticlopidine and PCR 4099), three cyclo-oxygenase inhibitors (aspirin, triflusal and indobufen) and a selective serotonin 5HT2 receptor antagonist (ketanserin) on platelet aggregation, in four platelet-dependent thrombosis models and on bleeding time. Platelet aggregation induced by ADP and collagen was completely inhibited by ticlopidine and PCR 4099 whereas only the collagen aggregation was reduced by the cyclo-oxygenase inhibitors. Ketanserin or a depletion of platelet serotonin by reserpine did not affect platelet aggregation. Ticlopidine and PCR 4099 greatly prolonged rat tail transection bleeding time. This is probably related to their known ability to inhibit ADP-mediated platelet aggregation. In contrast, the cyclooxygenase inhibitors did not affect bleeding time at all. Reserpine and ketanserin prolonged bleeding time by interfering with the action of serotonin on the vascular wall. Ticlopidine and PCR 4099 were very potent antithrombotics in all the models. Aspirin, only at a high dose, inhibited poorly thrombus formation on a silk thread in an arterio-venous shunt, suggesting that the inhibition of cyclo-oxygenase was not responsible. Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models. Ketanserin and reserpine reduced thrombus only in the metallic coil model. Thrombus formation was greatly reduced in fawn-hooded rats, which lack ADP in their platelet dense granules because of a genetic storage pool deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Conduction properties of spinal cord axons in the myelin-deficient rat mutant.

Spinal cords of myelin-deficient and normal age-matched (control) rats were removed and their conduction and pharmacological properties studied in an in vitro brain slice chamber. The conduction velocity of the myelin-deficient dorsal column axons was reduced to about 25% of control axons; however, the amyelinated myelin-deficient axons displayed refractory periods and the ability to sustain high-frequency action potential discharge similar to that of dorsal column axons in control rats. Pharmacological results suggest that the myelin-deficient dorsal column axons qualitatively express a normal complement of ion channels and receptors. The demonstration of a normal representation of channels and receptors on these axons supports the proposal that the oligodendrocyte, and not the axon, is the site of the primary defect in the myelin-deficient rat mutant. It is concluded that, unlike acutely demyelinated axons which display marked frequency-dependent conduction block, amyelinated axons of the myelin-deficient rat spinal cord develop compensatory mechanisms to stabilize action potential conduction.     

Comparison of antibody repertoires against Staphylococcus aureus in healthy individuals and in acutely infected patients

The management of staphylococcal diseases is increasingly difficult with present medical approaches. Preventive and therapeutic vaccination is considered to be a promising alternative; however, little is known about immune correlates of protection and disease susceptibility. To better understand the immune recognition of Staphylococcus aureus by the human host, we studied the antistaphylococcal humoral responses in healthy people in comparison to those of patients with invasive diseases. In a series of enzyme-linked immunosorbent assay analyses performed using 19 recombinant staphylococcal cell surface and secreted proteins, we measured a wide range of antibody levels, finding a pronounced heterogeneity among individuals in both donor groups. The analysis revealed marked differences in the antibody repertoires of healthy individuals with or without S. aureus carriage, as well as in those of patients in the acute phase of infection. Most importantly, we identified antigenic proteins for which specific antibodies were missing or underrepresented in infected patients. In contrast to the well-described transient nature of disease-induced antistaphylococcal immune response, it was demonstrated that high-titer antistaphylococcal antibodies are stable for years in healthy individuals. In addition, we provide evidence obtained on the basis of opsonophagocytic and neutralizing activity in vitro assays that circulating antistaphylococcal serum antibodies in healthy donors are functional. In light of these data we suggest that proper serological analysis comparing the preexisting antibody repertoires of hospitalized patients with different outcomes for nosocomial staphylococcal infections could be extremely useful for the evaluation of candidate vaccine antigens in addition to protection data generated with animal models.     

GABAergic control of the ascending input from the median raphe nucleus to the limbic system

The median raphe nucleus (MRN) is the primary source of serotonergic afferents to the limbic system that are generally considered to suppress hippocampal theta oscillations. GABA receptors are expressed in the MRN by serotonergic and nonserotonergic cells, including GABAergic and glutamatergic neurons. This study investigated the mechanisms by which the fluctuating GABA tone in the MRN leads to induction or suppression of hippocampal theta rhythm. We found that MRN application of the GABA(A) agonist muscimol (0.05-1.0 mM) or GABA(B) agonist baclofen (0.2 mM) by reverse microdialysis had strong theta promoting effects. The GABA(A) antagonist bicuculline infused in low concentrations (0.1, 0.2 mM) eliminated theta rhythm. A short period of theta activity of higher than normal frequency preceded hippocampal desynchronization in 46% of rats. Bicuculline in larger concentrations (0.5, 1.0, 2.0 mM) resulted in a biphasic response of an initial short (<10 min) hippocampal desynchronization followed by stable theta rhythm that lasted as long as the infusion continued. The frequency and amplitude of theta waves were higher than in control recordings and the oscillations showed a conspicuous intermittent character. Hippocampal theta rhythm elicited by MRN administration of bicuculline could be completely (0.5 mM bicuculline) or partially (1.0 mM bicuculline) blocked by simultaneous infusion of the GABA(B) antagonist CGP35348. Our findings suggest that the GABAergic network may have two opposing functions in the MRN: relieving the theta-generators from serotonergic inhibition and regulating the activity of a theta-promoting circuitry by the fluctuating GABA tone. The two mechanisms may be involved in different functions.     

Myocardial revascularization strategy in patients with acute coronary syndrome

Acute coronary syndrome (ACS) represents a spectrum of conditions caused by activated malignant coronary disease, with one of the following outcomes: stabilization, myocardial infarction or sudden death. The strategies of diagnostic procedures and treatment for ACS have been developed on the basis of differentiation between the two main groups of patients: those with unstable angina pectoris (UAP) and non-ST-segment elevation myocardial infarction (NSTEMI), and those with ST-elevation myocardial infarction (STEMI). The diagnosis and treatment of STEMI patients have both temporal and spatial limitations, where rapid identification and use of revascularization strategy, generally from 6 to not more than 12 hours, are the mainstay of the respective algorithm. In contrast to this, in UAP/NSTEMI patients the nature of the disease usually allows for more time for the diagnosis and choice of most appropriate therapy, whereas the chance of saving practically the entire myocardial area is much greater. Proposals of the possible algorithms for the procedures to be used in the diagnosis and management of ACS, based on the real possibilities available in the Republic of Croatia, and some our own results are presented in this review.     

Hyperglycaemia alters the endothelium-dependent relaxation of canine coronary arteries

The aim of the present study was to investigate the effects of experimental diabetes and hyperglycaemia per se on the endothelium-dependent relaxation of isolated canine coronary arteries and to analyse the possible involvement of the cyclooxygenase pathway in the alterations induced by hyperglycaemia. Rings from the left anterior descending coronary arteries of 18 metabolically healthy, six alloxan-diabetic and six insulin-treated alloxan diabetic dogs were set up for isometric tension recording. Diabetic coronaries as well as healthy vessels subjected to in vitro hyperglycaemia (25.5 mmol L-1 glucose) showed impaired (P < 0.05) relaxation to acetylcholine (3 nmol L-1-10 micromol L-1) compared with normoglycaemic, i.e. metabolically healthy and insulin-treated diabetic controls, either before or after indomethacin (3 micromol L-1) administration. The maximal dilation elicited by acetylcholine was further decreased (P < 0.05) by the cyclooxygenase inhibitor in the diabetic coronaries only. Relaxation to sodium nitroprusside did not differ among groups. These results suggest that hyperglycaemia may result in impaired endothelium-dependent dilation of coronary arteries. Diminished relaxation of diabetic coronaries is worsened by the inhibition of the synthesis of vasodilator cyclooxygenase products.     

Decomposing delta, theta, and alpha time-frequency ERP activity from a visual oddball task using PCA.

OBJECTIVE: Time-frequency (TF) analysis has become an important tool for assessing electrical and magnetic brain activity from event-related paradigms. In electrical potential data, theta and delta activities have been shown to underlie P300 activity, and alpha has been shown to be inhibited during P300 activity. Measures of delta, theta, and alpha activity are commonly taken from TF surfaces. However, methods for extracting relevant activity do not commonly go beyond taking means of windows on the surface, analogous to measuring activity within a defined P300 window in time-only signal representations. The current objective was to use a data driven method to derive relevant TF components from event-related potential data from a large number of participants in an oddball paradigm. METHODS: A recently developed PCA approach was employed to extract TF components [Bernat, E. M., Williams, W. J., and Gehring, W. J. (2005). Decomposing ERP time-frequency energy using PCA. Clin Neurophysiol, 116(6), 1314-1334] from an ERP dataset of 2068 17 year olds (979 males). TF activity was taken from both individual trials and condition averages. Activity including frequencies ranging from 0 to 14 Hz and time ranging from stimulus onset to 1312.5 ms were decomposed. RESULTS: A coordinated set of time-frequency events was apparent across the decompositions. Similar TF components representing earlier theta followed by delta were extracted from both individual trials and averaged data. Alpha activity, as predicted, was apparent only when time-frequency surfaces were generated from trial level data, and was characterized by a reduction during the P300. CONCLUSIONS: Theta, delta, and alpha activities were extracted with predictable time-courses. Notably, this approach was effective at characterizing data from a single-electrode. Finally, decomposition of TF data generated from individual trials and condition averages produced similar results, but with predictable differences. Specifically, trial level data evidenced more and more varied theta measures, and accounted for less overall variance.     

Dorsal raphe neurons: synchronous discharge with the theta rhythm of the hippocampus in the freely behaving rat.

1. Single-unit activity of 30 dorsal raphe (DR) neurons was recorded along with the cortical and hippocampal electroencephalogram and neck muscle electromyogram in freely behaving rats during sleep-waking states. 2. On the basis of firing rates, DR cells were divided into slow-firing (S-cells), fast firing (F-cells), and very fast firing (FF-cells) units. The S-cells (8 units) fired at rates of < 10 Hz, the F-cells (11 units) at 10-40 Hz, and the FF-cells (11 units) at 55-70 Hz. 3. The activity of 17 of 30 DR units was correlated with the theta rhythm of the hippocampus. They included both slow and rapidly firing DR neurons. These cells typically fired irregularly (single spikes or short-duration bursts of activity) during non-theta states of quiet waking and slow-wave sleep. With the change of behavioral state to awake-moving or rapid eye movement sleep, the activity of these units switched to a regular bursting pattern synchronous with the hippocampal theta rhythm. Seven of these 17 units were classified as theta-rhythmic cells on the basis of the tight phase-locking of their discharge to the hippocampal theta rhythm. The remaining 10 units were classified as theta-modulated cells on the basis of a smaller but significant coherence between unit discharge and the theta rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)