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Biomedical subjects

A Leon

Publications and source records attributed to A Leon.

At least 73 records · Page 4Linked to original sources

Anxiety psychopathology predictive of outcome in patients with panic disorder and depression treated with imipramine, alprazolam and placebo.

This study examines clinical predictors of outcome for patients with panic disorder and depression in a 16 week, placebo-controlled trial of alprazolam and imipramine (n = 126). Baseline global severity of illness and phobic avoidance were differentially predictive of acute response to treatment. Patients in the mild to moderate range of global distress experienced smaller degrees of improvement on alprazolam than on imipramine at week 4. At endpoint, the relative effectiveness of the active medication versus placebo was diminished in patients with higher levels of phobic avoidance. This relationship was not evident for completers, suggesting that the adverse effects of avoidance on outcome after sustained treatment was reduced.

Adult↗

Heat-loss response to a thermal challenge in seasonal affective disorder.

This study extends earlier findings of poorly facilitated postexercise heat loss during the winter in seasonal affective disorder (SAD). While depressed in the winter, 19 SAD subjects exhibited a significantly impaired postexercise heat loss relative to 10 control subjects. During the summer while euthymic, SAD subjects did not significantly differ from control subjects in postexercise heat loss. Since thermoregulatory heat loss is a highly dopamine-dependent process, these results support earlier findings of poorly facilitated dopamine availability in SAD during the winter and suggest a centrally mediated effect of light in SAD.

Adult↗

Extracorporeal photochemotherapy: evaluation of two techniques and use in connective tissue disorders.

Extracorporeal photochemotherapy (ECP) consists of collection of mononuclear cells, their irradiation with UV-A light in the presence of a photoactivable molecule--8-methoxy-psoralen (8-MOP) being the most widely used--and their reinjection into a patient. Two technical approaches have been developed. The photopheresis procedure involves four steps: (i) 8-MOP is given to the patient orally, 2 h before collection of white blood cells; (ii) a discontinuous flow cell separator (UVAR, Therakos, West Chester, PA, U.S.A.) is used for cell collection. The final product (740 mL) has a hematocrit of 4.5 +/- 1.7%); (iii) irradiation, performed with the same UVAR apparatus, begins before all the cells are collected, and lasts for 180 min after collection; and (iv) after irradiation, the buffy-coat is reinjected into the patient. We developed a technique summarized as follows: (i) mononuclear cell collection is performed using the Spectra (Cobe, Denver, CO, U.S.A.) cell separator, which provides a highly enriched mononuclear cell concentrate (always > 90% purity), in a small volume < 150 mL, subsequently adjusted to 300 mL for irradiation. Hematocrit of the final product is always < 2%. (ii) Soluble 8-MOP is added to the mononuclear cell concentrate at a final concentration of 200 ng/mL. (iii) Mononuclear cell concentrate is transferred in an EVA plastic bag (Macopharma, Tourcoing, France) to ensure an efficient irradiation with a UV irradiator (Vilber Lourmat, Marne-la-Vallée, France). (iv) After irradiation at 2 J/cm2 (time < 20 min), the cells are reinfused into the patient. Experimental and clinical data suggest that ECP has potential applications in the treatment of connective tissue disorders, such as systemic sclerosis and rheumatoid arthritis. Although encouraging data have been obtained, further clinical trials are warranted to establish the role of this therapy in these indications.

Animals↗

Dopamine and the structure of personality: relation of agonist-induced dopamine activity to positive emotionality.

Modern trait theories of personality include a dimension reflecting positive emotionality (PE) based on sensitivity to signals of incentive-reward. In animals, responsivity within an emotional system analog of PE is dependent on brain dopamine (DA) activity. To determine whether human PE trait levels are also associated with central DA, effects of a specific DA D2 receptor agonist were assessed in Ss who were widely distributed along the trait dimension of PE. The degree of agonist-induced reactivity in two distinct central DA indices was strongly and specifically associated with trait levels of PE, but not with other personality traits. The results suggest that the trait structure of personality may be related to individual differences in brain DA functioning.

Adult↗

N-acetylaspartylglutamate selectively inhibits neuronal responses to N-methyl-D-aspartic acid in vitro.

Canavan's disease is an autosomal recessive disorder characterized by a deficiency of aspartoacylase and accumulation of N-acetylaspartic acid (NAA), leading to a severe leukodystrophy and spongy degeneration of the brain. N-Acetylaspartylglutamate (NAAG), the presumed product of NAA, also accumulates in this disease. The endogenous dipeptide NAAG has been suggested to have low potency at NMDA receptors. Here we have tested the actions of NAAG and NAA on NMDA-evoked responses in cultured cerebellar granule cells. In differentiating granule cells grown in low-K+ medium, NAAG negated the survival-promoting effects of NMDA but not K+ depolarization. Neither NAAG nor NAA alone promoted cell survival in low-K+ medium. The modest trophic action of 50 microM kainic acid in low-K+ medium was reinforced by the NMDA receptor antagonist dizocilpine maleate and by NAAG. In K(+)-differentiated granule cells, NAAG raised the threshold of NMDA neurotoxicity but not that of kainate. The observed activities of NAAG were overcome by excess NMDA and were not mimicked by NAA. These data raise the possibility that disruption of NMDA receptor processes by NAAG may be of pathophysiological relevance.

Animals↗

Nerve growth factor and autoimmune diseases.

The initiation of a humoral immune response to a foreign antigen is a complex biologic process involving the interaction of many cell types and their secreted products. Autoimmune diseases, which are characterized by an abnormal activation of the immune system, probably result from the failure of normal self-tolerance mechanisms. The etiology of such illnesses, however, is far from being understood. While there have been extensive studies on the participation of the immune and endocrine systems in autoimmune diseases, few have dealt with nervous system-mediated immunoregulation in such situations. Evidence continues to grow suggesting that nerve growth factor (NGF), first identified for its activity in promoting the growth and differentiation of sensory and sympathetic neurons, may exert a modulatory role on neuroimmunoendocrine functions of vital importance in the regulation of homeostatic processes. Newly detected NGF-responsive cells belong to the hemopoietic-immune system and to populations in the brain involved in neuroendocrine functions. NGF levels are elevated in a number of autoimmune states, along with increased accumulation of mast cells. NGF and mast cells both appear to be involved in neuroimmune interactions and tissue inflammation. Moreover, mast cells themselves synthesize, store, and release NGF, proposing that alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature. This review focuses on these cellular events and presents a working model which attempts to explain the close interrelationships of the neuroendocrinoimmune triade via a modulatory action of NGF.

Autoimmune Diseases↗

[Prone position and operative posture in neurosurgery].

The most satisfactory method of prone positioning for the posterior approach to the spine and posterior fossa has been influenced by the necessity of providing good operating condition: prone position without abdominal and thoracic compression with a patient's head in the neutral position. Communication between the cava veins and the vertebral venous plexus explain that induce positioning can produce an excessive venous intraoperative bleeding with decreased surgical visibility. Furthermore venous return to the heart decreased resulting in some degree of impaired cardiac output. Hemodynamic disturbances of cerebral or spinal cord bloods flows can occurred.

Cerebrovascular Circulation↗

[Right ventricular function and postural changes during surgery of the lumbar spine].

The aim of the study was to assess the effects of the sitting prone position on right ventricular function in a group of patients requiring low back surgery with using of right heart catheterization with a low fast response thermodilution technique. This posture involves moderated hemodynamic effects. A discrete right ventricle impairment characterised by a decreased compliance was observed and may be due to a moderate compression by the sternum and was improved by fluid challenge. Thus, the sitting prone position appears a safe position.

Humans↗

[Changes in systolic pressure and posture in the surgery of the lumbar spine].

Anesthetized patients for lumbar disk surgery can be placed in prone or knee chest position which may adversely affect circulation. Augmentation of the delta-down component of the systolic blood pressure variation in ventilated patient is a sensitive indicator of intra operative hypovolemia. According to results, cardiac filling pressure is more affected in the knee chest position than in prone position. Preload state variation between the two positions, evaluated with albumin fluid challenge, seems to be more important than 500 ml.

Blood Pressure↗

Basic fibroblast growth factor modulates sensitivity of cultured hippocampal pyramidal neurons to glutamate cytotoxicity: interaction with ganglioside GM1.

Basic fibroblast growth factor (bFGF), a polypeptide originally identified as a mitogen for a variety of cells including astroglial cells, also exhibits neurotrophic (survival) effects on a number of neuronal populations, among the latter being hippocampal pyramidal cells. The present study investigated the effects of bFGF on the sensitivity of pyramidal neurons to the excitatory neurotransmitter, glutamate, and possible modulation by monosialoganglioside GM1. Cultures were generated from embryonic day 18 rat hippocampus, and first treated with bFGF at 4-5 days in vitro. Twenty-four hours later, cells were exposed to glutamate (100 microM-1 mM) for a further 24 h in the continued presence of bFGF. The cytotoxic action caused by 200-500 microM glutamate, which normally is present at this culture stage, was reduced by bFGF in a concentration- and time-dependent manner. GM1 (100 microM), given alone 2 h prior to glutamate, also limited this neuronal loss by 50-80%. At lower concentrations, neither bFGF (0.3 ng/ml) nor GM1 (1-10 microM) alone for 24 h was effective in altering neuronal sensitivity to glutamate. However, given together for 24 h these levels of bFGF and GM1 were almost as efficacious as bFGF alone at 3-10 ng/ml. Similar results were obtained with more mature (12 day) cultures. The ability of GM1 to modulate trophic factor actions towards excitatory amino acids makes gangliosides useful tools in the study of central nervous system plasticity and repair processes.

Animals↗

A proposed autacoid mechanism controlling mastocyte behaviour.

Evidence is provided here supporting the existence of a novel autacoid mechanism negatively modulating mast cell behaviour in response to noxious stimuli in vivo; hence, the denomination "autacoid local inflammation antagonism" (ALIA). In particular, as lipid amides of the N-acylethanolamine type have been reported to accumulate in tissues in degenerative inflammatory conditions, we examined whether these N-acylated lipids could exert regulatory effects on mast cell activation in vivo. The results reported show that both long- and short-chain N-acylethanolamines, when systemically administered, are effective in reducing mast cell degranulation induced by local injection of substance P in the ear pinna of developing rats. These and other data suggest that the endogenous production of N-acylethanolamines may constitute a local autocrine/paracrine response for the negative feedback control of mast cell responses to various activating signals. Such a process may be of physio-pathological relevance in the regulation of functional neuro-immune-mast cell interactions.

Animals↗

Influence of depression on the treatment of panic disorder with imipramine, alprazolam and placebo.

This paper presents findings from a multisite study of 126 subjects meeting DSM-III-R criteria for Panic Disorder who also met criteria for a concurrent Major Depressive Episode, Dysthymia, or Depressive Disorder NOS. The study's primary aim was to discern the influence of varying degrees of depression on the comparative efficacy of alprazolam, imipramine and placebo on anxiety outcomes. A placebo-controlled, double-blind, parallel random assignment design was utilized over a total of 16 weeks. There was no medication effect on panic outcomes. At endpoint, percent of anticipatory anxiety (i.e., time spent worrying about having an anxiety attack) was significantly lower in the patients taking active medications vs. placebo. Phobic measures were significantly improved by alprazolam, vs. both imipramine and placebo early in the study; however, by week 8 both active medications were equally superior to placebo in the reduction of phobic symptoms. In addition, both active medications were significantly more effective than placebo in reducing depression. The same efficacy pattern (i.e., active medications superior to placebo) was observed on measures of general functioning. Importantly, there were no significant interactions observed between medication and presence of major depression on the depression measures, indicating that both alprazolam and imipramine were equally efficacious in treating the depression in patients with panic disorder and major depression. Since the patients enrolled in this study suffered from major depressive disorder in the mild to moderate severity range, these results may not be transferrable to patients with panic disorder and severe major depression.

Adult↗

Successful treatment of HIV-related vasculitis with peripheral neuropathy with short-term steroids followed by the association of zidovudine and plasmapheresis.

OBJECTIVE: treatment of HIV-related vasculitis, avoiding prolonged immunosuppressive therapy. DESIGN: prospective pilot study of HIV-related neurological vasculitis. PATIENTS: two HIV-infected patients with histologically proven vasculitis. INTERVENTION: short-term corticosteroid followed by zidovudine combined with plasmapheresis. MAIN OUTCOME MEASURES: clinical, biological, immunological and electromyographic evaluation. RESULTS: complete neurological recovery. CONCLUSION: excellent tolerance and efficacy of combined zidovudine and plasmapheresis therapy in peripheral neurological HIV-related vasculitis.

AIDS-Related Opportunistic Infections↗

A randomized, prospective comparison of anterior and posterior approaches to radiofrequency catheter ablation of atrioventricular nodal reentry tachycardia.

BACKGROUND: Two different techniques have been developed for radiofrequency catheter ablation of typical atrioventricular nodal reentry (AVNRT). Lesions made anteriorly near the apex of the triangle of Koch usually eliminate fast pathway function, whereas lesions made posteriorly near the ostium of the coronary sinus selectively affect slow pathway function. The current study compares the safety, efficacy, and electrophysiological effects of these two techniques in a prospective, randomized fashion. METHODS AND RESULTS: Fifty consecutive patients with typical AVNRT were randomly assigned to receive radiofrequency lesions either anteriorly (n = 22) or posteriorly (n = 28). If the initial approach failed to eliminate inducibility of AVNRT after 1 hour or 10 applications of radiofrequency energy, the alternative ablation technique was used. Patients underwent repeat electrophysiological testing 48 hours and 3 months after ablation. The primary success rates of the anterior and posterior techniques were similar (55% versus 68%, p = NS). All of the patients who failed the initial approach were successfully treated by the alternative technique without developing high-grade atrioventricular block. One patient developed right bundle branch block during an anterior lesion, and another patient developed complete atrioventricular block as the result of a posterior lesion. CONCLUSIONS: The posterior approach to radiofrequency catheter modification of the atrioventricular node is as effective as the anterior approach, and both techniques are associated with a low risk of complications. As long as AVNRT persists, it appears safe to cross over from one technique to the other.

Adult↗

Treatment of polyarteritis nodosa related to hepatitis B virus with short term steroid therapy associated with antiviral agents and plasma exchanges. A prospective trial in 33 patients.

OBJECTIVE: To test the effectiveness and tolerance of antiviral agents associated with short term immunosuppression in the treatment of polyarteritis nodosa (PAN) related to hepatitis B virus (HBV). METHODS: We conducted a prospective, nonblinded, multicenter trial in which patients with multisystemic PAN related to HBV were included. Every patient initially underwent a short term (2 weeks) treatment with prednisone and then received vidarabine (Vira A) and plasma exchanges. The end point of the study was control of the disease (recovery or remission) or death. RESULTS: Thirty-three patients were included. Every patient had histopathologic or arteriographic evidence of vasculitis and was infected with actively replicating HBV. Disease activity during the first 6 months was controlled in 26 patients (78.8%). Among the 25 patients still alive at the end of the study, 24 (72.7%) had completely recovered with no clinical or laboratory evidence of systemic vasculitis after at least 18 months without treatment. Eight patients died during the study period; 3 of treatment failure, usually early in the course of the disease. One patient died of fulminant hepatitis 3 months after the entry in the study at time of seroconversion. The survival curve showed that at 7 years, 76% of the patients were alive. HBeAg/anti-HBeAb seroconversion was observed in 12 patients (36.3%) after one Vira A cycle. When a 2nd cycle of Vira A or alpha interferon was prescribed, HBeAg/anti-HBeAg seroconversion occurred in 15 patients (45.4%). Two other patients who underwent a 2nd cycle of Vira A administration, had lost HBeAg and no longer expressed serological evidence of replication as assessed by HBV DNA spot hybridization. At the end of the study, 17 (51.5%) no longer expressed serological evidence of HBV replication. This treatment was effective and only minor side effects were noted. CONCLUSIONS: We conclude that this new therapeutic approach to PAN related to HBV effectively controlled systemic vasculitis and was associated with a higher number of recoveries from chronic HBV infections. The development of new antiviral agents, such as interferon alpha 2b, allows us to hope that antiviral therapy will have a role to play as a first line treatment regimen of virus induced vasculitis.

Adult↗

Time course of nigrostriatal system changes after tract hemisection and effects of ganglioside treatment: a multiple retrograde fluorescent tracing study.

The postlesion phenomena of nigrostriatal neurons following partial tract hemisection have been studied with retrograde axonal transport of dyes in rats treated with saline or GM1 ganglioside (30 mg/kg, i.p., daily for varying times). The time course of the plastic changes in both experimental animal groups was determined by a double retrograde fluorescent tracing technique, utilizing Fast blue (FB) as prelesion tracer, and Diamidino yellow (DY) as postlesion tracer. The data show that the number of nigral cells retrogradely labeled by the prelesion intrastriatal injection of FB declined progressively to 50% of their initial number over 3 weeks. The ganglioside treatment did not significantly influence this temporal pattern of labeled cell loss. By DY-labeling, an almost complete block of the retrograde axonal transport was observed up to 1 week postlesion and only after 3 weeks a partial recovery was evident, positively influenced by the GM1 treatment. Therefore, together with the findings on nigrostriatal cell loss, these data indicate that ganglioside treatment favors and/or accelerates the recovery of axonal transport of surviving nigral neurons but does not significantly affect their degenerative rate in the first 3 weeks after the lesion.

Amidines↗