[Tridimensional theory of personality: applications to substance abuse disorders]. / Teoría tridimensional de la personalidad: aplicación a los trastornos por abuso de sustancias.

INTRODUCTION: We have assessed the weight that Cloninger' dimensions play in the substance abuse disorder. Also, we have analysed the hypothetical self-independence of these dimensions and if there is some correlation between those and some demographic variables. METHODOLOGY: 20 drug abstinents and 20 controls, all males, fulfilled the Tridimensional Personality Questionnaire. RESULTS: All the values on the Novelty Seeking (NS) subclass and the overall NS scale were higher in the abstinent group. The most meaningful differences were found on the excitable and extravagant subclass and the total NS scale. There was also a significant though smaller difference on the disorderly subclass. Only the Harm Avoidance (HA) subclass fatigability was significantly higher in the abstinent group. The value of persistence substantially low in the abstinent subjects was the most significant difference between groups when the Reward Dependence (RD) scale was considered. The correlation analysis demonstrated that the three dimensions were mutually independent in the controls. However, in the abstinent group NS correlated positively with HA and negatively with persistence. Any correlation was found between the dimensions and the demographic variables in both groups. CONCLUSION: A high sensation seeking behaviour and a low persistence seems to be the most prominent characteristic of our abstinent subjects. Both tendencies could explain in part their high substance seeking tendency and possibly the high rate of relapse found in similar populations. Finally, the Cloninger's hypothesis about the mutually independence of the dimensions seems to be fulfilled only in the control group.

Teoría tridimensional de la personalidad: aplicación a los trastornos por abuso de sustancias / Tridimensional theory of personality: applications to substance abuse disorders

Introducción: Hemos valorado el peso que las dimensiones de Cloninger desempeñan en el desorden de abuso de sustancias, y analizado la hipotética independencia de estas dimensiones entre sí y si mantienen alguna correlación con variables demográficas. Metodología: 20 abstinentes a las drogas y 20 controles, todos varones, completaron el Cuestionario Tridimensional de Personalidad. Resultados: Todos los valores de la escala de Buscador de Novedad (BN) fueron superiores en el grupo abstinente. Las diferencias más notables fueron las correspondientes a las subescalas 'excitable' y 'extravagante'; también obtuvimos una significativa, aunque menor diferencia en la subescala 'desordenado'. En la escala 'Evitación de Daño' (ED) sólo 'fatigabilidad' fue significativamente superior en el grupo abstinente. Con respecto a la 'Dependencia de Recompensa' (DR), el valor de la subescala 'persistencia' fue sin embargo sustancialmente menor en los sujetos abstinentes. El análisis de correlación demostró que las tres dimensiones eran mutuamente independientes en los controles. Sin embargo, en el grupo abstinente BN correlacionó positivamente con ED y negativamente con 'persistencia'. No se encontró ninguna correlación entre las dimensiones y las variables demográficas en ambos grupos. Conclusiones: Un elevado comportamiento buscador de sensaciones y una baja persistencia parecía ser la característica principal de nuestros sujetos abstinentes. Ambos parámetros explicarían en parte su elevada tendencia a buscar sustancias y posiblemente la alta tasa de recaídas encontrada en poblaciones similares. Finalmente, indicar que la hipótesis de Cloninger acerca de la mutua independencia de las dimensiones se cumplía sólo en el grupo control (AU)

Endothelial activation and cytokine expression in human acute cardiac allograft rejection.

By extrapolation from the responses of cultured human umbilical vein endothelial cells (EC) and bovine aortic EC to short-term cytokine stimulation, EC activation is postulated as a likely component of the host response in acute allograft rejection and cardiac transplant-associated accelerated arteriosclerosis. To investigate the extent to which EC activation occurs in vivo in humans and to identify potential targets for therapeutic interventions, we compared the phenotypic characteristics of vascular EC as seen during clinicopathologically significant vs non-significant acute cardiac allograft rejection. We used monoclonal and monospecific polyclonal antibodies to coagulation molecules [tissue factor, thrombomodulin (TM), antithrombin III (AT-III), fibrinogen/fibrin, cross-linked fibrin and von Willebrand factor (vWF)], adhesion molecules (P-selectin, ICAM-1) and major histocompatibility complex (MHC) class I and II molecules. In addition we sought evidence of local cytokine production (IL-1, IL-2R, IL-4, IL-6, IL-7, IL-8, TNF-alpha, PDGF-AA, PDGF-BB), which might mediate alterations in expression of these proteins. We found that in clinically significant grades of cardiac allograft rejection requiring increased immunosuppression, in contrast to lesser grades of rejection not requiring clinical intervention, there was increased microvascular EC activation and differential expression of cytokines. EC changes associated with more extensive cardiac allograft rejection requiring treatment included: (i) disruption of the normal anticoagulant state with downregulation of TM and AT-III, upregulation of tissue factor and vWF expression, and associated extensive fibrin deposition; (ii) upregulation of MHC class I antigens, which are potential targets for host cytotoxic T lymphocytes; (iii) increased expression of the leucocyte adhesion molecules P-selectin and ICAM-1; (iv) expression of the pro-inflammatory cytokines IL-1 beta and TNF-alpha; and (v) increased expression of PDGF-AA and BB, which are known to promote migration and proliferation of intimal cells, and hence may contribute to development of transplant-associated atherosclerosis. Collectively these findings suggest that immune events resulting in EC surface changes and/or production of key cytokines play a role in the pathogenesis of acute transplant rejection and may contribute to the long-term complication of accelerated arteriosclerosis in allograft coronary arteries.

Analysis of proliferating cell nuclear antigen expression aids histological diagnosis and is predictive of progression of human cardiac allograft rejection.

A quantitative immunohistological analysis was undertaken of 558 sequential paraffin-embedded and 22 snap-frozen endomyocardial biopsies (EMBs) from nine consecutive patients undergoing cardiac transplantation and followed for up to 1 year post-surgery. Serial monitoring was performed to assess whether 1) the phenotypic characteristics, 2) level of immune activation, or 3) expression of proliferation-associated antigens by intragraft leukocytes were useful in determining the grade of rejection or predicting further rejection episodes. Particular attention was given to those patients whose most recent EMBs showed grade 2 rejection, because these patients present a common problem in clinical management wherein a decision must be made as to whether or not to increase immunosuppression. Comparison of EMBs displaying various grades of rejection showed that whereas the absolute number of leukocytes (CD45), memory T cells (UCHL1/CD45RO), helper T cells (OPD4), and macrophages (Mac387) increased with increasing grade of rejection, the proportions of each subset remained similar. Cell proliferation was determined by labeling with monoclonal antibodies to proliferating cell nuclear antigen (cyclin) and Ki-67, and immune activation was assessed using an anti-interleukin-2 receptor (CD25) monoclonal antibody. The numbers of intragraft proliferating cell nuclear antigen-positive Ki-67+ or interleukin-2 receptor-positive cells were found to increase with increasing grades of rejection. Moreover, comparison of EMBs with equivalent histological features of rejection (grade 2) showed significantly (P < 0.0001) greater numbers of proliferating cell nuclear antigen-positive cells in EMBs preceding an episode of higher grade or persisting rejection versus EMB from patients whose rejection resolved, as seen on subsequent biopsy, without increased immunosuppression. These data suggest that the identification of proliferating or immunologically activated cells may aid in the histological diagnosis of clinical rejection and provide a valuable indicator predictive of likely further rejection episodes of increasing severity if grade 2 rejection is left untreated.

Mechanism of a clinically relevant protocol to induce tolerance of cardiac allografts. Perioperative donor spleen cells plus cyclosporine suppress IL-2 and interferon-gamma production.

Many groups have reported that preoperative injection of donor-derived whole spleen cells or major histocompatibility complex antigens prolongs organ allograft survival in experimental models, but the immunosuppressive mechanism(s) responsible remains unclear. A central, confounding issue is how to reconcile documentation of comparable levels of mRNA for IL-2 in suppressed versus control groups with obvious host hyporesponsiveness. We used a model of tolerance induction involving perioperative injection of donor spleen cells and injection of CsA at day 2 after transplant to analyze the serial expression of several proinflammatory cytokines relevant to development of alloresponsiveness within cardiac allografts and recipients' spleens. Four experimental groups of Lewis rats receiving vascularized heterotopic cardiac allografts from Brown Norway (BN) donors were evaluated: (1) untreated controls; (2) animals receiving intraoperative injection of donor BN spleen cells; (3) those receiving a single injection of CsA on day 2 post-Tx; and (4) animals given the combination of intraoperative BN spleen cells and CsA on day 2 post-Tx. Graft survival was significantly prolonged in Lewis rats receiving the combined spleen cell/CsA therapy (mean 64 days, with 40% of grafts surviving > 100 days, n = 15) compared with acute rejection at about 8 days (range 6-13, n = 20) in each of the 3 control groups (P < 0.0001). By comparison with acutely rejecting allografts in the control untreated group at day 7 post-Tx, allografts in rats receiving the combined perioperative spleen cell/CsA treatment showed (1) significantly reduced graft cellularity and interstitial edema; (2) significantly decreased features of immune activation, including infiltration by mononuclear cells expressing IL-2R or proliferating cell nuclear antigen; (3) decreased intragraft expression of the cytokines IL-2 and IFN-gamma; and (4) suppression of endothelial activation as evidenced by both failure of up-regulation of intracellular adhesion molecule-1 and maintenance of thrombomodulin expression by graft endothelium. Analysis of sections of recipients' spleens showed that spleen cell/CsA therapy led to significant reductions versus untreated controls, in expression of IL-2, IFN-gamma, and IL-2R. Similarly, mixed lymphocyte response cultures showed that responder cells from rats receiving combined therapy proliferated by 93-95% less than untreated animals. Our results suggest that the efficacy of this clinically relevant protocol is associated with suppression of IL-2 or IFN-gamma protein production, and that in the absence of such molecules, it appears that T cell-receptor occupancy by alloantigens readily induces a state of anergy in vivo.

Neuroretinitis in acquired syphilis.

Syphilitic disease of the retina and/or the optic nerve head, without choroidal involvement, occurred in our 4 cases and in another 19 cases. The condition almost always takes place in the secondary stage, frequently associated with meningitis, and rarely in tertiary meningovascular syphilis. Fluctuating visual loss and floating spots without ocular pain are the presenting symptoms. Retinitis, papillitis, and neuroretinitis are accompanied by an inflammatory reaction in the vitreous and, sometimes, in the aqueous. Paracentral scotomas and blind spot enlargement, related with posterior pole and papillary edema, are the most usual visual field defects. Almost complete visual recovery is the rule in the treated cases, although in some instances cystoid macular edema and retinal ischemia due to endarteritis cause permanent visual loss. Treatment with crystalline penicillin is mandatory in patients with concomitant neurosyphilis, whereas procaine penicillin is seemingly sufficient in those with a normal cerebral spinal fluid examination.

An approach to the antiinflammatory activity of borjatriol.

The antiinflammatory activity of borjatriol (a diterpenoid isolated from SIDERITIS MUGRONENSIS Borja) was tested using the cotton pellet-granuloma assay. The compound inhibited the granuloma weight and the serum lysozyme activity in a dose-dependently way. The determination of this enzyme has allowed us to distinguish between an irritant (carrageenan) which reduces the granuloma weight and antiinflammatory substances (phenylbutazone and borjatriol).