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Biomedical subjects

C Papageorgiou

Publications and source records attributed to C Papageorgiou.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Simulated generation of evoked potentials components using networks with distinct excitatory and inhibitory neurons.

Long latency evoked potentials (EP's) are electrical potentials related to brain information processing mechanisms. In this paper, three-layered neurophysiologically based artificial neural network model is presented whose neurons obey to Dale's law. The first two layers of the network can memorize and recall sparsely coded patterns, oscillating at biologically plausible frequencies. Excitatory low-pass filtering synapses, from the second to the third layer, create evoked current dipoles, when the network retrieves memories related to stimuli. Based on psychophysiological indications, simulated intracranial dipoles are straightforwardly transformed into long latency EP components such as N100 and P300 that match laboratory-measured scalp EP's.

Biomedical Engineering↗
PubMed2000

Prenatal diagnosis of epignathus in the first half of pregnancy: a case report and review of the literature.

Congenital teratomas of the oral cavity commonly present as tissue masses projecting from the mouth. The important prognostic determinants are: the age of presentation, technical problems during surgical removal of the mass, associated anomalies, and the nature of the composing tissues. This study reports one case of epignathus (an extremely rare oropharyngeal teratoma) that was diagnosed by ultrasonography at 19 weeks of gestation and reviews the relevant literature.

Adult↗
PubMed1999

The observer perspective: biased imagery in social phobia, agoraphobia, and blood/injury phobia.

Clark and Wells' (1995): 'A cognitive model of social phobia'. In Social phobia: Diagnosis, assessment, and treatment (pp. 69-93), R. G. Heimberg, M. R. Liebowitz, D. A. & F. R. Hope (eds.); cognitive model of social phobia proposes that social phobics generate a negative impression of how they appear to others. This impression often occurs in the form of an image from an "observer" perspective in which social phobics can see themselves as if from another person's vantage point. This study investigated the specificity of the observer perspective among patients with social phobia, agoraphobia, and blood/injury phobia. All participants were asked to recall and imagine a recent anxiety-provoking social situation and a non-social/non-anxiety-provoking situation, and rate their perspective for each. Consistent with predictions only patients with social-evaluative concerns (social phobics and agoraphobics) reported observer perspectives for anxiety-provoking social situations. Only social phobics showed a significant shift from an observer to a field perspective across the two conditions. The clinical implications of these findings are briefly discussed.

Adult↗
PubMed1999

Cerebrospinal fluid levels of biotin in various neurological disorders.

OBJECTIVES: To analyse biotin concentrations in human cerebrospinal fluid (CSF) and serum from controls without evidence of nutritional or neurological disorders and patients with common neurological disorders. PATIENTS AND METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, serum was prepared from freshly drawn whole blood and biotinidase in samples was inhibited before being analysed for biotin by radioligand assay. RESULTS: Assay characteristics were within an acceptable range (intra-and interassay coefficient of variations were 8.8 and 12.0 respectively, recovery: 91-114% and sensitive, lowest standard concentration 15 ng/l). Significantly lower values for biotin were found in patients with multiple sclerosis (both CSF and serum) in comparison to the controls. Significantly reduced values for cerebrospinal fluid biotin were found in epileptics compared to controls, whereas, in serum the difference was approaching significance. No significant differences were observed in other groups of patients. CONCLUSION: There is a significant reduction in cerebrospinal fluid biotin in epileptics and patients with multiple sclerosis compared to controls. In epileptics this may be related to competition between biotin and anticonvulsants bearing carbamide ring for absorption. Reduction of biotin levels in patients with multiple sclerosis could be attributed to intestinal malabsorption caused by the underlying disease or a biotin-binding immunoglobulin which may be involved in multiple sclerosis pathogenesis.

Adult↗
PubMed1999

Our experience in laparoscopic diagnosis and management in women with chronic pelvic pain.

Chronic pelvic pain (CPP) still remains a serious problem in everyday gynecological practice. The aim of this study was to prospectively estimate the occurrence of pelvic varicosities in women with CPP and also to report our experience in the establishment of diagnosis and management of patients with CPP. We examined 264 premenopausal women aged 18 to 42 years referred to us for chronic constant pelvic pain of at least 6 months duration and with incomplete relief by previous treatments. The women were divided into 4 groups in proportion to their parity. The results of our study demonstrate that pelvic congestion is a common finding in women with chronic pelvic pain especially in multigravidas. Based on our findings we support laparoscopic resetting of the uterus as an option for treatment in patients desiring maintenance of future fertility.

Adolescent↗
PubMed1998

Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations.

T-cell immunosuppressant-based therapies efficiently control early graft rejection in allotransplantation settings. They fail, however, to prevent those rejection events which are mediated by transplant-induced antibody (Ab) responses such as those involved in xenograft and chronic allograft rejection. This is mainly due to their inability to block T-cell-independent Ab production against the transplanted organs. The bioactive metabolite 2(Z) of leflunomide (1) inhibits the formation of such Ab, but the drug has pharmacokinetic properties and a therapeutic window incompatible with transplantation indications. Pyrazole 3, a constrained analogue of 2(Z), was designed and shown to be conformationally and biologically similar to 2(Z). Further investigations with derivatives of 3 demonstrated that the pyrazoles had very tight structure-activity relationships, the only equipotent compound being 3o. However, in contrast to 2(Z), both 3 and 3o were inactive in vivo due to short half-life and drug concentrations lower than the in vitro obtained IC50 values. Compound 3o inhibits T-cell-independent Ab production by a different biochemical mechanism from that of 2(Z) and 3 and may therefore represent a valuable tool for the identification of new targets for B-cell inhibition.

Administration, Oral↗
PubMed1998

Isoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach.

A library of thioamide derivatives of leflunomide 1a and of its bioactive metabolite 1b has been synthesised on solid phase. Thus, para-substituted phenylacetic acids were coupled to TentaGel and were subsequently reacted with aromatic isothiocyanates. Treatment of the resulting enaminothioamides with hydroxylamine led to their simultaneous cyclisation and cleavage from the resin affording 2-25. Their in vitro profiling demonstrated that the amide-thioamide isologous substitution was detrimental of the biological activity.

Animals↗
PubMed1998

Side effects of brequinar and brequinar analogues, in combination with cyclosporine, in the rat.

Brequinar is an immunosuppressant with the potential to be combined with cyclosporine in synergistic combination therapy. The drug tends to accumulate when given daily per os, and pharmacokinetic interaction with cyclosporine appears to enhance toxicity. Analogues with similar immunosuppressive activity have been identified at Du Pont Merck Pharmaceutical Co., that do not accumulate upon daily oral dosing in rats, and hence could have an improved potential in combination treatment with cyclosporine. We performed a toxicity study with brequinar and two brequinar analogues, administered orally once daily for 4 weeks, either alone or in combination with cyclosporine (Neoral, Novartis Pharma AG). In a first study relatively high doses were evaluated with cyclosporine at non-toxic doses of 5 and 10 mg/kg/d. The maximum tolerated dose of brequinar alone was estimated between 5 and 10 mg/kg/d; that of the analogues was estimated between 10 and 20 mg/kg/d, and above 20 mg/kg/d, respectively. In combination with cyclosporine at 5 and 10 mg/kg/d, approximately a 2-fold reduction in the maximum tolerated dose was observed. In a second study lower doses were evaluated in combination with cyclosporine at 2.5 and 5 mg/kg/d. Also this study revealed increased toxicity of brequinar (analogues) when given in combination with cyclosporine. The side effects observed were typical for drugs in the brequinar class and included leukocytopenia and thrombocytopenia, reduced body weight gain or body weight loss, thymic atrophy, cellular depletion of bone marrow and splenic white pulp, and villous atrophy in jejunum. Concentrations of brequinar (analogues) were determined in blood sampled 4 h after administration at day 1, 14 and 21-28 of the experiment. There was a tendency for drug accumulation in some groups treated with brequinar and cyclosporine. For one of the analogues at a low dose, higher concentrations were measured in groups treated with combinations of this compound and cyclosporine. We conclude that a potential synergism in immunosuppression using combinations of brequinar (analogues) and cyclosporine can be complicated by enhanced toxicity of the compounds. This indicates the need for a careful evaluation of the therapeutic window in a combined treatment together with detailed pharmacokinetics.

Administration, Oral↗
PubMed1998

Fasciculation potentials in healthy people.

The aim of this study was to investigate the fasciculation potentials (FPs) in the small-peripheral muscles of the foot and hand and the possible associated factors, in a healthy population. One hundred-twenty-two normal individuals (65 men and 57 women), aged 17-67 years (mean 39.96, SD=12.76) participated in the study. A special questionnaire consisting of 47 questions was devised as the basic instrument of the interview, which included the Hamilton anxiety rating scale. The extensor digitorum brevis (EDB), the flexor hallucis brevis (FHB) and the first dorsal interosseous (FDI) muscles were studied bilaterally using surface electrodes. In 94 (58 men and 36 women) from 122 participants (65 men and 57 women) FPs were recorded (men 89.2%, women 63.1%, all 77%). The mean FPs per minute and muscle, in all three muscles, was 8.0 (SD=4.6). More FPs were recorded in the muscles of foot than in FDI (p<0.01) and in FHB than in EDB (p<0.001). FPs were correlated to gender, body height and weight and to the score of the Hamilton scale (r2>0.1, p<0.01). The syndrome of benign FPs was observed in 2 men (1.6% of men). These results suggest that FPs are a very common phenomenon in the peripheral muscles of healthy persons.

Action Potentials↗
PubMed1998

Subcortical frontal lesions on MRI in patients with motor neurone disease.

MRI was performed in 32 patients with motor neurone disease (26 men and 6 women, aged 40-77 years) and in a control group of 21 subjects. Of the patients studied, 19 had definite and 11 probable amyotrophic lateral sclerosis (ALS) and two had progressive bulbar palsy. In 10 patients there were asymmetrical bilateral foci of increased signal intensity on proton-density and T2-weighted images, confined to the white matter. Two patients had only cortical frontal atrophy and slightly increased ventricular size, whereas 20 had normal MRI. The focal lesions were not confined to corticospinal tracts, but were also observed in subcortical frontal areas. While the lesions along the corticospinal tracts correspond to pyramidal tract degeneration, the subcortical foci correlate with degeneration of the frontal bundles and indicate generalised involvement of the central nervous system.

Adult↗
PubMed1998

Relationships between worry, obsessive-compulsive symptoms and meta-cognitive beliefs.

The present study had two principal aims. First, the overlap between the revised Padua Inventory (PI-WSUR) a measure of obsessive-compulsive symptoms (Burns et al., 1996) and worry was assessed. Second, the relationship between meta-cognitive beliefs, proneness to pathological worry and obsessive-compulsive symptoms was explored when controlling for the interdependency of worry and obsessive-compulsive measures. The results indicate that whilst the PI-WSUR shows reduced overlap with the Penn State Worry Questionnaire, there are still problematic levels of overlap with a more content-based measure of worry. Results of multiple regression analyses demonstrated that specific sets of meta-cognitive beliefs were associated with worry proneness and obsessive-compulsive symptoms. The present data are consistent with recent formulations of generalized anxiety disorder and obsessive-compulsive disorder.

Adult↗
PubMed1998

Effects of attention training on hypochondriasis: a brief case series.

BACKGROUND: Empirical evidence indicates that manipulations of attention may facilitate changes in cognition and stress symptoms in emotional disorder. METHODS: The present study reports the effects of Attention Training (ATT) in a brief case series of three patients with primary hypochondriasis using an A-B-A design. RESULTS: ATT produced clinically significant improvements in self-reported measures of affect, and illness-related behaviour and cognition. Treatment gains were maintained at 6 months follow-up assessments. Measures of body-focused attention indicated that the ATT procedure acted on attentional processes as intended. CONCLUSIONS: The present case series extends the effects of ATT to problems of hypochondriasis. A number of studies now suggest that ATT is associated with a reduction in anxiety and negative beliefs across disorders of panic, social phobia and hypochondriasis. Controlled clinical trials are now required to establish firmly the effects of ATT as a component of cognitive therapy.

Aged↗