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)     

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.     

Currant allergy and the Rosaceae-grass pollen allergy syndrome: a case report.

BACKGROUND: Despite the increasing use of currants in culinary recipes, currant allergy has rarely been reported. OBJECTIVES: To study a case of currant allergy and to explore cross-reactivity between grass pollen and Rosaceae family fruit allergens. METHODS: Skin prick tests to pollen and skin prick-to-prick tests with currants and peach were performed. Specific IgE levels were determined using the CAP method. We prepared a protein extract of 0.1 mg/mL in phosphate-buffered saline using red currant in the presence of protease inhibitors. Immunoblot inhibition studies were performed to explore cross-reactivity between grass pollen and currant allergens. RESULTS: Skin prick test results were positive to Dactylis, arizonic, and olive pollens. Results of skin prick-to-prick tests with fresh red and black currants were negative and positive, respectively, to peach. The specific IgE level was 5.7 KU/L to red currant and 2.92 KU/L to peach (CAP). Western blot analysis with red currant extract revealed specific IgE protein bands of 37 and 26 kDa. Preincubation of sera with extracts from red currant and peach inhibited both IgE bands, and preincubation with Dactylis pollen inhibited the 37-kDa band only. CONCLUSIONS: We report a case of allergy to grass pollen with an oral allergy syndrome involving several fruits from 2 different families of the Rosidae subclass confirmed by in vitro tests. Inhibition studies demonstrated cross-reactivity between different fruits (currant and raspberry) from the Rosidae subclass and were incomplete with grass pollen allergens.     

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.     

Infravesical obstructive uropathy secondary to extreme vulval atrophy

Lower urinary tract obstruction in women is an uncommon condition resulting from multiple either organic or functional disorders. This paper contributes one case of obstructive uropathy secondary to presence of almost complete vulvar synechia due to extreme genital atrophy, a rare entity that may appear in postmenopausal women. Partial and incomplete vulvar fusion usually occurs in significant postmenopausal atrophies, sometimes associated to urethral meatus stricture; this, however, has no significant repercussion on urination dynamics. No other comparable case was found in the reviewed literature.     

The antithrombotic efficacy of the GP IIb/IIIa antagonist SR121787 is potentiated by antithrombin-dependent factor Xa inhibition without an increase in the bleeding risk in the rabbit

Current antithrombotic therapy in acute coronary symptoms is only partially effective and exhibits bleeding complications. These experiments were designed to address the antithrombotic and hemorrhagic interactions of the novel glycoprotein (GP) IIb/IIIa antagonist SR121787 in combination with the indirect inhibitor of factor Xa, SR90107/ORG31540. Thrombogenesis was initiated by electrolytic injury of the intimal surface of the carotid artery, and thrombus formation was assessed by recording carotid blood flow and by measuring thrombus weight 45 min after electrical stimulation. SR121787 was an efficacious antithrombotic agent in this model (ED50 = 16.3+/-0.3 mg/kg, p.o.), whereas heparin (4.5 mg/kg, i.v.) and SR90107/ORG31540 [1 mg/kg (850 aXa anti-units/kg), i.v.] were only marginally effective (17 and 27% inhibition of carotid blood flow reduction, respectively). Coadministrations of heparin (4.5 mg/kg, i.v.) or SR90107/ORG31540 (0.5 mg/kg, i.v.) were found to potentiate the antithrombotic efficacy of threshold doses of SR121787 (5 or 10 mg/kg, p.o.). The enhancement of the antithrombotic efficacy of SR121787 by SR90107/ORG31540 was--contrary to the association of SR121787 with heparin--not accompanied by an increased blood loss from the incised rabbit ear. Coadministrations of heparin or SR90107/ORG31540 did not influence the ex vivo antiaggregatory activity of SR121787. SR121787 coadministration did not alter the systemic anticoagulant activities in heparin or SR90107/ORG31540-treated animals. These data suggest the potential for optimized antithrombotic treatment in acute coronary syndromes when a GP IIb/IIIa antagonist (SR121787) is combined with an antithrombin-dependent factor Xa inhibitor (SR90107/ORG31540).