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Biomedical subjects

C Papageorgiou

Publications and source records attributed to C Papageorgiou.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1998

Evaluation of first-trimester screening by fetal nuchal translucency and maternal age.

The aim of this screening study was to evaluate first-trimester screening for chromosomal defects by fetal nuchal translucency thickness at 10-14 weeks of gestation in four Fetal Medicine Units in Greece. Estimates of the risk for trisomy 21 were calculated taking into account fetal nuchal translucency thickness and maternal age. There were 3550 cases; the median maternal age was 29 years (range 16-48 years); and 277 (7.8 per cent) were over 37 years. The median crown rump length was 60 mm (range 38-85 mm) and the fetal nuchal translucency thickness increased with crown rump length and measurements were above the 95th centile in 101 (2.9 per cent) of the cases. The adjusted risk was 1 in 300 or more in 172 (4.9 per cent) of the cases and the high-risk group contained ten of the 11 (91 per cent) fetuses with trisomy 21 and all 11 fetuses with other chromosomal defects. The findings of this study provide further evidence for the high efficacy of screening for chromosomal abnormalities by fetal nuchal translucency and maternal age.

Adolescent↗
PubMed1998

Correlation between denervation activity and compound muscle action potential amplitude in hereditary motor and sensory neuropathy I and II.

Studying the electrophysiological characteristics of the various types of Charcot-Marie-Tooth disease is important in the understanding of its pathophysiology. The purpose of this study was to identify the frequency of fibrillation potentials and positive sharp waves (FP/PWs) in HMSN I and II and, since they are indices of denervation, to elucidate whether they are correlated with the amplitude of compound muscle action potentials (CMAP). We reviewed the electrophysiological findings of 47 patients who have been studied in our hospital and found to suffer from Charcot-Marie-Tooth polyneuropathy. FP/PW were graded according to a 4-grade scale and the 38 m/sec criterion for motor conduction velocity (MCV) was used for distinction between HMSN I and II subgroups. Seventy percent of HMSN II patients and 81% of HMSN I patients showed fibrillation potentials in the upper or lower limbs. There was no difference in the frequency of FP/PW appearance between the two groups. In the HMSN II group the FP/PW grade correlated with CMAP amplitude in the upper limbs. In both groups there was no correlation between FP/PW grade and MCV. Our findings might indicate that in HMSN I there is a considerable axonal destruction that occurs concurrently with myelin loss.

Action Potentials↗
PubMed1997

Essential trace element alterations in amyotrophic lateral sclerosis.

Although trace elements have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) for a long time, new evidence has connected familial ALS with the metalloenzyme copper-zinc superoxide dismutase, thus reinforcing the study of their metabolism. This work presents the results of serum and cerebrospinal fluid levels of copper, zinc, manganese and magnesium, by atomic absorption spectrophotometry. Statistically significant decreased cerebrospinal fluid and serum copper levels were found in patients compared to the control group (20.25 +/- 7.09 vs. 30.86 +/- 16.02 SD micrograms/l and 913.21 +/- 165.55 vs. 1020.17 +/- 197.76 SD micrograms/l) while serum manganese levels were found to be increased in patients (3.59 +/- 0.89 SD micrograms/l) compared to controls (3.03 +/- 1.23 SD micrograms/l). Zinc and magnesium levels were unchanged. Our findings indicate an essential trace element imbalance in the disease.

Adult↗
PubMed1997

Changes of presaccadic cortical activity when performing horizontal, visually guided saccades.

When a visually guided saccade task is running, the presaccadic potential obtained in the initial period of the task differs from those obtained later, while the subject's oculomotor performance remains unaffected. These time-related changes of cortical activity consist both of an overall decreasing electrical activity as well as a selective one over certain cortical areas. The generalised reduced activity already described in earlier studies is considered as an unspecified effect such as fatigue or decreased motivation. On the contrary, the pronounced selective changes of cortical activity obtained over cortical areas such as the centro-parietal and frontal cortices, should be related with more specific, that is, visuomotor function. We assume that at the beginning of the task of the performance of the saccade needs the activation of several cortical areas but later on the same oculomotor plan runs sufficiently under subcortical control.

Adult↗
PubMed1997

Conformational control of cyclosporin through substitution of the N-5 position. A new class of cyclosporin antagonists.

Cyclosporin A (CsA) can be regiospecifically alkylated at the NH of Val-5 with reactive bromides in the presence of phosphazene-base P4-t-Bu to yield derivatives 2-5. These are devoid of immunosuppressive activity in vitro but they have binding affinity for cyclophilin A (CypA) similar to that of CsA and thus represent a new class of cyclosporin antagonists. 1H NMR (DMSO-d6) studies have shown that the compounds exist in a single, all trans conformation. A comparison of this NMR data with X-ray crystallographic analysis of a CypA/CsA derivative complex demonstrates that the solution structure does not correspond to the bioactive conformation.

Cyclosporine↗
PubMed1997

Ascorbate in healthy subjects, amyotrophic lateral sclerosis and Alzheimer's disease.

The aim of the present study was to report the levels of ascorbic acid in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) and the effectiveness of ascorbic acid homeostasis in the central nervous system. Plasma and CSF ascorbic acid levels were measured by high performance liquid chromatography in 19 ALS patients, 17 AD patients and 15 controls. No statistically significant difference was found between patients and controls. However, wide fluctuations of plasma concentrations were found to result in relatively stable CSF levels, by appropriate adjustments of CSF/plasma ratio. It appears that in normal subjects and in the disease under study, this ratio reflects the activity of the choroid plexus ascorbate transporter.

Alzheimer Disease↗
PubMed1997

Cognitive function in non-demented individuals complaining of short-term memory disturbances: a study with event-related potentials (P 300) and brain CT scan.

Event-related potentials (ERPs) were elicited in 30, non-consecutive, non-demented individuals, complaining of short-term memory disturbances. Fifteen of them had a moderate diffuse cerebral atrophy on their brain CT and the other 15 had a negative brain CT. ERPs were also elicited in 15 age-matched controls with no reported memory disturbances and negative brain CTs. The statistical analysis showed that the group of individuals with cerebral atrophy had a significantly prolonged P300 (P3) latency and a decreased P3 amplitude compared to controls. It is concluded that among persons complaining of short-term memory disturbances, the individuals who show cerebral atrophy, taken as a group, have a P3 latency prolongation and/or low P3 amplitude a finding which reflects an impaired information processing.

Adult↗
PubMed1996

Prenatal diagnosis of X-linked spinal and bulbar muscular atrophy in a Greek family.

X-linked spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disorder which is caused by an expansion of the trinucleotide repeat (CAG)n in the first exon of the androgen receptor gene. Two cases of prenatal testing for the disease in a Greek family are reported. An affected male died in his late 50s of this disorder and his 30-year-old daughter (an obligate carrier) asked for prenatal testing for SBMA. DNA analysis revealed that she indeed carried an expanded allele of 40 repeats, as well as a normal size allele of 24 repeats. Prenatal diagnosis of SBMA was performed when, on two successive pregnancies, two male fetuses with the expanded (CAG)n allele were found.

Adult↗