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Biomedical subjects

C Papageorgiou

Publications and source records attributed to C Papageorgiou.

At least 19 recordsLinked to original sources
PubMed2003

Psychophysiological correlates in male to female transsexuals studied with a P300 investigation.

BACKGROUND: Transsexualism is thought to be related to cortical processes reflecting a complex mosaic of biological, psychological and social/cultural information. Since the P300 component of event-related potentials is considered as an index of attentional processes, the present study focuses on auditory P300 elicited during a short memory test in male to female (MF) transsexuals, compared with that in healthy controls. METHOD: The P300 component was evaluated during the anticipatory period of a short memory test in 13 MF transsexuals who had a gender reassignment operation, at least 3 years previously (mean time 17-6 years, range 3-31 years) and 26 healthy subjects (11 males and 15 females) matched for age and educational level. RESULTS: MF transsexuals exhibited significant reduction of P300 amplitude in the left frontal and temporoparietal areas in comparison to the control group. Furthermore, the group of transsexuals showed a significant delay of P300 latency in comparison to the controls, at the central frontal region. CONCLUSIONS: These findings point to significant psychophysiological alterations of distributed cortical circuits in MF transsexuals. These alterations may be critically related to the biological substrate of MF transsexualism.

Attention↗
PubMed2002

Frontal lobe dysfunction in amyotrophic lateral sclerosis.

The aim of the present study was to investigate the involvement of frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS) using ocular motor paradigms and neuropsychological testing. Fifty-one patients with ALS participated in the following ocular motor tasks: (1) a three-choice task and (2) a remembered saccade task. The patients underwent a clinical and neuropsychological evaluation. One-third of ALS patients presented with signs of frontal dysfunction, as determined by their high distractibility factors (DF) in the three-choice task and their performances in both the Wisconsin and Stroop tests. ALS patients exhibited longer latencies to eye movement than controls in the performance of the remembered saccade task, specifically in performance of both remembered and delayed saccades, but saccade accuracy was not impaired. Finally, performance indices of the ocular motor tasks, in particular the DF, was correlated only with the degree of dysarthria.

Aged↗
PubMed2002

Thyroid gland neurofibroma in a NF1 patient.

Neurofibromas are a hallmark of neurofibromatosis type 1 (NF1). They are usually benign and rarely present in the thyroid gland region. There is a suspected association between NF1 and intramedullary thyroid carcinoma and there is a well-known association between NF1 and pheochromocytoma. Here, we present a 55-year-old man with typical symptoms of NF1, whose course was complicated by a neurofibroma of the thyroid gland. His clinical spectrum of symptoms included bilateral cataract established before the age of 35 years, quadriparesis and an intrathoracic mass. The patient died because of abdominal carcinomatosis of unknown origin. The rarity of thyroid gland neurofibroma is discussed here, emphasizing the importance of early detection of these and other NF1 complications, also including the risk of malignant transformation with lethal outcome.

Abdominal Neoplasms↗
PubMed2001

Comparative efficacy of mycophenolate sodium (MPS) and mycophenolate mofetil (MMF) with and without cyclosporine in rat transplantation models.

BACKGROUND: ERL is the enteric-coated sodium salt of mycophenolic acid, presently in clinical development. The drug substance mycophenolate sodium (MPS) was evaluated in rat transplantation models and compared with mycophenolate mofetil (MMF) for therapeutic window and synergy with cyclosporine (CsA). METHODS: Allotransplantation was performed in the Dark Agouti-to-Lewis (DA-to-Lewis; kidney, heart, and aorta) and Brown Norway-to-Lewis (BN-to-Lewis; kidney) strain combinations, and hamster heart xenotransplantation was performed in athymic and euthymic Lewis rats. The compounds were administered daily orally, starting the day of transplantation. RESULTS: In kidney and heart transplantation the minimal efficacious dose of CsA was 5.0 mg/kg/d. For MPS this dose was 10 mg/kg/d in BN-to-Lewis kidney transplantation, 20 mg/kg/d in DA-to-Lewis heart transplantation, and 10 mg/kg/d in hamster-to-athymic rat heart transplantation. At these doses the first signs of adverse effects were evident, indicating a narrow therapeutic window. No window was established for MMF in these models or for MPS in DA-to-Lewis kidney transplantation. There was no potential synergy between CsA and MPS or MMF regarding efficacy, but fewer side effects were noted in efficacious combinations, in particular for MPS. In aorta transplantation, MPS and MMF dose-dependently inhibited intima thickening. The combination of 20 mg/kg/d MPS and 10 mg/kg/d CsA gave long-term survival of hamster-to-rat xenografts. CONCLUSIONS: Despite the overall comparable efficacy and narrow therapeutic window of MPS and MMF when given alone, MPS apparently is better tolerated than MMF in some of the transplant models. The combination of these agents with CsA allows fine-tuning between optimal immunosuppression and adverse side effects.

Animals↗
PubMed2001

Impaired P600 in neuroleptic naive patients with first-episode schizophrenia.

Deficits of working memory (WM) are recognized as an important pathological feature in schizophrenia. Since the P600 component of event related potentials has been hypothesized that represents aspects of second-pass parsing processes of information processing, and is related to WM, the present study focuses on P600 elicited during a WM test in drug-naive first-episode schizophrenics (FES) compared to healthy controls. We examined 16 drug-naive first-episode schizophrenic patients and 23 healthy controls matched for age and sex. Compared with controls schizophrenic patients showed reduced P600 amplitude on left temporoparietal region and increased P600 amplitude on left occipital region. With regard to the latency, the patients exhibited significantly prolongation on right temporoparietal region. The obtained pattern of differences classified correctly 89.20% of patients. Memory performance of patients was also significantly impaired relative to controls. Our results suggest that second-pass parsing process of information processing, as indexed by P600, elicited during a WM test, is impaired in FES. Moreover, these findings lend support to the view that the auditory WM in schizophrenia involves or affects a circuitry including temporoparietal and occipital brain areas.

Acoustic Stimulation↗
PubMed2001

Abnormal P600 in heroin addicts with prolonged abstinence elicited during a working memory test.

The P600 component of event-related potentials, believed to be generated by anterior cingulate gyrus and basal ganglia, is considered as an index of aspects of second-pass parsing processes of information processing, having much in common with working memory (WM) systems. Moreover, dysfunction of these brain structures as well as WM deficits have been implicated in the pathophysiology of opioid addicts. The present study is focused on P600 elicited during a WM test in twenty heroin addicts with prolonged abstinence compared with an equal number of healthy controls. The results showed significantly prolonged latencies at right hemisphere, specifically at Fp2 abduction. Moreover, memory performance of patients did not differ from that of normal controls. These findings may indicate that abstinent heroin addicts manifest abnormal aspects of second-pass parsing processes as are reflected by the P600 latencies, elicited during a WM test. Additionally, the P600 might serve as a valuable investigative tool for a more comprehensive understanding of the neurobiological substrate of drug abuse.

Adult↗
PubMed2001

Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.

The prevention of xenograft rejection is substantially dependent on inhibiting antibodies (Ab) produced by B-cells independently of T-cell signals (TI-1). Due to their ubiquitous biochemical mechanisms of action, the immunosuppressants currently employed not only fail to discriminate between B- and T-cells but also have a narrow therapeutic window and, thus, their prolonged use in complex immunosuppressive regimens is problematic. By capitalizing on the target enzyme-bound (DHODH) structure 1b of one of these compounds, leflunomide, and modulating part of its multiple mechanisms of action to gain selectivity, the quinoline-8-carboxamide 3 was designed as a potentially weak enzyme inhibitor but effective immunosuppressant. Compound 3 fulfilled the mechanistic criteria set and had 10-fold B-cell over T-cell selectivity. Its pyridyl analogue 4 was found to be a highly potent and selective B-cell immunosuppressant with a 75-fold selectivity for B- over T-cells (as judged by the MLR data) and no general cytotoxicity at concentrations up to 160-fold higher than those required to inhibit B-cells. In the mouse, 4 effectively blocked TI-1 Ab production and suppressed Ab-mediated xenograft rejection in a xenotransplantation model under a once-daily dosing regimen, with efficacy down to 0.3 mg/kg/day po. These are the first data demonstrating the feasibility of the development of drugs specific for impeding Ab production.

Animals↗
PubMed2001

Tolerability profile of sodium mycophenolate (ERL080) and mycophenolate mofetil with and without cyclosporine (Neoral) in the rat.

Mycophenolic acid sodium salt (ERL080) is currently in Phase III clinical trials for the prophylaxis of kidney transplant rejection upon coadministration with Neoral (cyclosporin A microemulsion). To assess the relative side effect profile of ERL080 and MMF as drug substances in Lewis rats, a rat strain commonly used in transplantation experiments, a comparative 4-week tolerability study was performed. Escalating doses of ERL080 and MMF were administered orally at 10-30 mg/kg/d (i.e., doses within or above the immunosuppressive range in rats), either in single compound treatment or in combination with cyclosporine (CsA) at a daily oral dose of 7.5 mg/kg. The compounds were well tolerated as documented by body weight monitoring, hematologic parameters, and weight and histology of organs. Major abnormalities observed were a dose-dependent reduction in thymus weight associated with immunosuppression, in some cases villous atrophy in the jejunum, a reduction in white blood cell counts and lymphocyte counts (mean value in distinct treatment groups not exceeding 40-50%), a decrease in red blood cell counts and hemoglobin concentration (at maximum 25-30%), and an increase in platelet counts (in some groups up to doubling). At a given dose, these adverse effects were slightly more pronounced for MMF than for ERL080, and for groups under CsA coadministration compared to both compounds given alone. No significant potentiation effect of CsA on the changes induced by ERL080 or MMF was observed. Moreover, there were no new toxic entities evident upon CsA microemulsion coadministration.

Animals↗
PubMed2001

Brief cognitive therapy for social phobia: a case series.

Social phobia is a common and disabling anxiety disorder. The most effective psychological treatments for social phobia are cognitive therapy and exposure. However, the degree of improvement across these treatments is variable, and their implementation is costly and time-consuming. This study aimed to conduct a preliminary clinical evaluation of the effectiveness of a brief, new form of cognitive therapy based on a recent cognitive model of social phobia. Six consecutively referred patients with social phobia were treated using established single case series methodology. Brief cognitive therapy was effective with all patients demonstrating clinically significant improvements in all measures. Treatment gains were maintained at follow-up. The mean number of treatment sessions delivered was 5.5 and improvements compare favourably with previous treatment studies. Brief cognitive therapy for social phobia appears promising and it is potentially cost-effective. Future randomised and controlled evaluations of this brief treatment are warranted.

Adolescent↗
PubMed2001

Social phobic interoception: effects of bodily information on anxiety, beliefs and self-processing.

It has been suggested that body-state information influences self-perception and negative thinking in social phobia [Clark, D. M., & Wells, A. (1995). A cognitive model of social phobia. In R. G. Heimberg, M. R. Liebowitz, D. A. Hope & F. R. Schneier (Eds.), Social phobia: diagnosis, assessment and treatment (pp. 69-93). New York: Guilford Press.]. This study explored the effects of body-state information on anxiety and cognition in patients with generalised social phobia during a feared social interaction. It was hypothesised that information concerning an increase in pulse rate would lead to increments in anxiety, negative beliefs and self-processing whilst information concerning a decrease in pulse rate would have the opposite effect. The results of this study were generally consistent with the hypotheses. These findings are important as they may help to account for fluctuations in anxiety, negative beliefs and self-processing in social situations that do not present objective social threat. In particular, social anxiety appears to be modulated by body-state information. The implications of the present findings for cognitive therapy of social phobia are briefly discussed.

Adolescent↗
PubMed2001

Frontal-parietal activation differences observed before the execution of remembered saccades: an event-related potentials study.

Healthy subjects performed saccadic eye movements in one memory (MEM) and two delay tasks (delay, DEL and modified delay, M-DEL) while we recorded scalp event-related potentials (ERPs) from 25 electrode sites. In the MEM task the subjects were instructed to retain in memory the location of a visual target for a delay of 1-6 s and then perform a remembered saccade at the go signal. In the DEL task the target remained on until movement completion and in the M-DEL task the target, that was visible during the delay period, disappeared synchronously with the go signal. A reduction in response latency and an increase in the percentage of dysmetric movements were observed for the MEM task compared to the two delay tasks. An increased ERP activity at the central-frontal electrode sites compared to the parietal sites was significant only for the MEM task early on during the delay period (500-1000 ms). During the period preceding the onset of the saccade, a parietal increase of activity was observed for all tasks. Furthermore the activity was smaller for the frontal compared to the parietal areas only for the memory task thus indicating a near reversal of the previous pattern of activity observed during the early delay period. This specific activation pattern of frontal and parietal areas, observed for the MEM task only, requires further investigation focusing on the temporal pattern of activation of large brain areas involved in working memory processing.

Electroencephalography↗
PubMed2001

Enterohepatic recirculation: a powerful incentive for drug discovery in the inosine monophosphate dehydrogenase field.

With the exception of organ transplant immunosuppression, the treatment of various IMPDH-dependent hyperproliferative diseases by MPA has failed due to the drug's EHC-induced GIT adverse effects. To influence its therapeutic index, novel formulations such as gastro-resistant MPA-Na (ERL080) or MPA/cholestyramine combinations have been developed. Structurally novel IMPDH inhibitors have been discovered based on high throughput screening (pyridazoles) and rational design (methoxyphenyloxazoles). The clinical data on methoxyphenyloxazole derivatives such as VX-497 that is not expected to undergo EHC, will bring improved understanding of the relationship between IMPDH blockade and GIT toxicity.

Cyclooxygenase Inhibitors↗
PubMed2000

Peroneal nerve palsy following knee dislocation: pathoanatomy and implications for treatment.

Peroneal nerve palsy following knee dislocation is a serious problem, and neurolysis at the time of knee reconstruction does not always result in return of peroneal nerve function. We describe peroneal nerve pathoanatomy in three patients in whom late exploration of the peroneal nerve was performed because of ongoing absence of ankle dorsiflexion. We identified frank nerve rupture in two patients and a lengthy neuroma in continuity in one which extended far proximal to the fibular head and well above the previous surgical incision used for peroneal nerve neurolysis at the time of knee reconstruction. In light of the current state of microneural surgery and the potential to reconstruct nerve defects, we discuss how our findings impact on treatment, and provide recommendations which may improve recovery of peroneal nerve function in future cases.

Adult↗