Antiplatelet and antithrombotic activities of essential oil from wild Ocotea quixos (Lam.) Kosterm. (Lauraceae) calices from Amazonian Ecuador.

Ocotea quixos essential oil was shown to possess significant inhibitory activity of platelet aggregation and clot retraction in rodent plasma. This study is aimed at fully characterizing the antiplatelet activity of the whole essential oil and its main components trans-cinnamaldehyde and methyl cinnamate also in human plasma, at investigating the mechanism underlying such activity and at evaluating the potential antithrombotic activity of subacute treatment of mice with Ocotea essential oil. In vitro Ocotea essential oil and trans-cinnamaldehyde inhibited arachidonic acid-, U46619-, ADP-, phorbol12-myristate13-alcetate-, collagen-induced platelet aggregation and thrombin-induced clot retraction in human and rodent plasma; Ocotea oil and trans-cinnamaldehyde competitively antagonized contractions induced by thromboxane A2 receptor agonist U46619 in rat isolated aortic ring (K(B) = 18 and 3.2 microg ml(-1), respectively). In vivo Ocotea oil, orally administered in a subacute treatment (30-100 mg kg(-1) day(-1) for 5 days) to mice, prevented acute thrombosis induced by collagen-epinephrine intravenous injection. This antithrombotic activity was not accompanied by pro-haemorragic side effect, as detected by the inactivity in bleeding test, thus showing a favourable safety profile compared to the conventional antiplatelet agent, acetylsalicylic acid. Present findings indicate that Ocotea essential oil possesses potent and safe antithrombotic activity attributable to its antiplatelet and vasorelaxant effects. The main constituent trans-cinnamaldehyde seems to be the primary responsible for this activity through a putative mechanism involving the inhibition of thromboxane A2 receptors.     

Platelet transfusions are not associated with increased morbidity or mortality in cardiac surgery

PURPOSE: To determine the independent relationship between leukoreduced platelet transfusions and adverse events in cardiac surgery. METHODS: In this observational study, detailed baseline and perioperative data were prospectively collected on consecutive patients who underwent cardiac surgery at a single institution from 1999 to 2004. The independent associations of platelet transfusion with clinical outcomes (low output syndrome, myocardial infarction, stroke, renal failure, sepsis, and death) were determined by multivariable logistic regression analysis and propensity score case-control analysis. RESULTS: Of the 11,459 patients analyzed, 2,174 (19%) received (leukoreduced) platelets - 1,408 received 5 U, 471 received 10 U, 140 received 15 U, and 155 received 20 or more units. Although all measured adverse event rates were higher in those who received platelets, in neither the logistic regression analyses nor the propensity score analyses was there any association between platelet transfusion and any of the adverse events. CONCLUSIONS: Transfusion of leukoreduced platelets in cardiac surgery is not associated with adverse clinical outcomes when adjustments are made for important confounders.     

Epilepsy and family expressed emotion: results of a prospective study.

PURPOSE: To verify the emotional components expressed by the relatives of adult patients with a diagnosis of epilepsy, and whether they are related to adjustment to the illness and the course of the illness over time. METHODS: We studied a consecutive sample of 43 outpatients suffering from epilepsy and 43 key relatives using the Camberwell Family Interview (CFI), with the expressed emotion (EE) of the relatives being rated at baseline (T0). EE refers to a construct representing some key aspects of interpersonal relationships: the relatives were assigned to the high-EE group if they scored 3 or more on the emotional over involvement (EOI) scale, or showed hostility, or made 6 or more critical comments. The patients were clinically evaluated at baseline and for 1 year of appropriate treatment by an epileptologist who was blinded to the EE ratings. They also completed STAI XI, STAI X2 and Beck's Depression Inventory at baseline. RESULTS: Twenty-six relatives (60%) were rated as showing a high degree of EE. In the 12-month follow-up study, high EE and high EOI were found to be associated with a significantly higher seizure frequency than that recorded for the patients living in low-EE households (p<0.05). The patients from households assessed as reflecting a high degree of criticism showed poor drug compliance (p<0.01), whereas those with relatives assessed as having a high degree of warmth showed better clinical and pharmacological compliance (p<0.01). High family criticism scores also correlated with higher study entry levels of depression (p<0.05) and trait and state anxiety (p<0.05) among the patients. CONCLUSIONS: The study findings highlight the impact of particular components of the family emotional climate on the clinical course and psychological adjustment of patients with epilepsy.     

Interleukin-6 gene alleles affect the risk of Alzheimer's disease and levels of the cytokine in blood and brain

Two different polymorphic regions of the interleukin-6 (IL-6) gene were investigated in patients with Alzheimer's disease (AD) and non-demented controls. The -174 C allele in the promoter region of IL-6 gene was over-represented in AD patients compared to controls and significantly increased the risk of AD. Moreover, the -174 CC genotype was associated with a high risk of the disease in women. The D allele of a variable number of tandem repeat (VNTR) was in strong linkage disequilibrium with the -174 C allele and slightly increased AD risk. On the other hand, the frequency of the VNTR C allele was decreased in patients with AD and was negatively associated with the risk of developing AD. Both the -174 CC and VNTR DD genotypes were also associated with increased IL-6 levels in the blood and brain from AD. These findings suggest that IL-6 may play a multifaceted role in AD by affecting the turnover of the cytokine.     

Contact heat evoked potentials to painful and non-painful stimuli: effect of attention towards stimulus properties

The study aim was to evaluate the effect of different attentional tasks on the amplitudes and latencies of painful and non-painful contact heat evoked potentials (CHEPs). CHEPs were recorded in 12 healthy subjects during two experimental conditions, in which attention was oriented towards the intensity and the distress caused by the stimuli and were compared with CHEPs recorded during a neutral condition. The painful heat stimulation produced a negative potential at Cz vertex with a latency around 540 ms (Cz/N540), a positive peak at Cz electrode around 730 ms (Cz/P730) and, lastly, a positive peak around 1000 ms (Pz/P1000) in the Pz traces. The Cz/P730 wave was significantly higher in amplitude only during the painful stimulation and is probably related to coding the nociceptive activity. Varying the attentional target towards different properties of the stimulus did not cause any significant change in CHEP responses amplitude and latencies compared with the neutral condition. Our results suggest that CHEPs represent a reliable functional measure of the nociceptive pathways and that they are generated by the activation of different cerebral areas involved in pain processing. The high activation level of each of these area or their spatial neighbouring might explain the strong similarity of CHEP components recorded during different attentional manipulations.     

Gastrointestinal mesenchymal tumors - immunophenotypic classification and survival analysis

The current definition of gastrointestinal tumors (GIST) as CD117-positive mesenchymal tumors of uncertain malignant potential fails to include a number of cases with similar histology. In an attempt to improve the classification of these neoplasms, we conducted an immunohistochemical analysis of 244 mesenchymal tumors with histological features of GIST. According to their immunophenotype, the tumors were classified as GISTs, which are characterized by CD117 (c-kit) expression; gastrointestinal CD117-negative CD34 positive stromal tumors (GINST); alpha-smooth muscle actin and/or desmin positive gastrointestinal leiomyogenic tumors (GILT); S-100 and glial fibrillary acidic protein positive gastrointestinal glial/schwannian tumors (GIGT); gastrointestinal neuronal/glial tumors (GINT), which are positive for S-100/glial fibrillary acidic protein plus neuronal/glial markers; and gastrointestinal fibrous tumors (GIFT), which are only vimentin positive. The most common type of tumors were GIST, followed in order of frequency by GINST, GILT, GIGT, GIFT, and GINT. GISTs did not show any preferential location, whereas GINSTs occurred almost exclusively in the stomach and duodenum, and GILTs preferentially in the large intestine. Over a median follow-up period of 71 months, malignant behavior, i.e., metastatic spread, was observed in all tumor types except GINTs. Malignancy was associated with distal gut location, high mitotic activity, large tumor size, and nuclear pleomorphism, though none of these criteria alone discriminated between benign and malignant. Kaplan-Meier analysis of disease-specific survival showed significant differences in the long-term outcome of the newly defined subgroups. We conclude that, despite strong morphological similarities, gastrointestinal mesenchymal tumors are heterogeneous in their immunophenotype and biology.     

Dipolar sources of the early scalp somatosensory evoked potentials to upper limb stimulation Effect of increasing stimulus rates

Brain electrical source analysis (BESA) of the scalp electroencephalographic activity is well adapted to distinguish neighbouring cerebral generators precisely. Therefore, we performed dipolar source modelling in scalp medium nerve somatosensory evoked potentials (SEPs) recorded at 1.5-Hz stimulation rate, where all the early components should be identifiable. We built a four-dipole model, which was issued from the grand average, and applied it also to recordings from single individuals. Our model included a dipole at the base of the skull and three other perirolandic dipoles. The first of the latter dipoles was tangentially oriented and was active at the same latencies as the N20/P20 potential and, with opposite polarity, the P24/N24 response. The second perirolandic dipole showed an initial peak of activity slightly earlier than that of the N20/P20 dipolar source and, later, it was active at the same latency as the central P22 potential. Lastly, the third perirolandic dipole exaplaining the fronto-central N30 potential scalp distribution was constantly more posterior than the first one. In order to evaluate the effect of an increasing repetition frequency on the activity of SEP dipolar sources, we applied the model built from 1.5-Hz SEPs to traces recorded at 3-Hz and 10-Hz repetition rates. We found that the 10-Hz stimulus frequency reduced selectively the later of the two activity phases of the first perirolandic dipole. The decrement in strength of this dipolar source can be explained if we assume that: (a) the later activity of the first perirolandic dipole can represent the inhibitory phase of a “primary response”; (b) two different clusters of cells generate the opposite activities of the tangential perirolandic dipole. An additional finding in our model was that two different perirolandic dipoles contribute to the centro-parietal N20 potential generation. Received: 5 August 1997 / Accepted: 26 November 1997     

Walking modality affects respiratory muscle action and contribution to respiratory effort

We hypothesized that walking at increased speed or increasing gradient might have different effects on chest wall kinematics and respiratory muscle power components, and contribute differently to respiratory effort sensation. We measured the volumes of chest wall compartments by optoelectronic plethysmography, esophageal, gastric and transdiaphragmatic (P _di) pressures, and the sensation of the respiratory effort by a Borg scale in five normal subjects walking both at ascending gradient with constant speed (AG) and at ascending speed with constant gradient (AS). Chest wall kinematics, evaluated by displacement of chest wall compartments, did not show any significant difference between AS and AG. Muscle power, calculated as the product of mean flow and mean pressure, increased similarly, but its partitioning into pressure and velocity of shortening differed in the two modes. A greater increase in the pressure developed by the abdominal muscles (P _abm) (4.06-fold), and in the velocity of shortening of both rib cage inspiratory muscles (v _rcm,i) (2.01-fold) and the diaphragm (v _di) (1.90-fold) was associated with a lower increase in the pressure developed by the rib cage inspiratory muscles (P _rcm,i) (1.24-fold) and P _di (0.99-fold) with AG. Instead, with AS, a lower increase in P _abm (2.12-fold), v _rcm,i (1.66-fold) and v _di (1.54-fold) was associated with a greater increase in P _rcm,i (1.56-fold) and P _di (1.97-fold). A combination of P _abm and v _di during AG (Wald ²=23.19, P<0.0000), with the addition of P _rcm,i during AS (Wald ²=29.46, P<0.0000), was the best predictor of Borg score. In conclusion, the general strategy adopted by respiratory centers during different walking modes does not differ in terms of ventilation, chest wall kinematics, and respiratory muscle power production, whereas it does in terms of partitioning of power into pressure and velocity of shortening, and respiratory muscle contribution to respiratory effort sensation. Combinations of different patterns of flow and pressure generation made the respiratory effort sensation similar during AS and AG modes.     

Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients

Background  

We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma.