Biomedical subjects

A Papadimitriou

Publications and source records attributed to A Papadimitriou.

At least 37 records · Page 2Linked to original sources

PubMed2003

Clinical characteristics of the alpha-synuclein mutation (G209A)-associated Parkinson's disease in comparison with other forms of familial Parkinson's disease in Greece.

An Ala53Thr mutation of the alpha-synuclein has been recently identified as a rare cause of familial Parkinson's disease (fPD). In the present study, the clinical characteristics of Parkinson's disease (PD) patients with Ala53Thr alpha-synuclein mutation (alpha-synPD) were compared with fPD patients without any known mutation. An investigator blinded to the results of the genetic analysis examined 15 alpha-synPD patients and 43 consecutive fPD patients. Demographic data, age at onset of the illness, duration of the disease and modality of presentation were collected. Segregation ratios for both sexes in individuals at risk of developing alpha-synPD were estimated. The Unified Parkinson's disease rating scale (UPDRS) was also completed. The 15 alpha-synPD patients were matched for duration of the disease and age at onset with 15 of the 43 fPD patients (MfPD). Comparisons were also made between 14 patients belonging to three multicase families with patterns of inheritance similar to alpha-synPD. The alpha-synPD patients were significantly younger (mean difference 11.8 years) and showed the first sign of the disease earlier in life (mean difference 12.7 years) as compared with the fPD patients. Tremor at onset was present in only one (6.7%) of the alpha -synPD patients compared with 18 (41.9%) of the fPD patients (P = 0.01). At the time of examination rigidity, postural instability, orthostatic hypotension and the overall clinical severity did not differ significantly either between alpha-synPD and fPD or between alpha-synPD and MfPD groups. Nevertheless, some clinically relevant trends concerning the psychiatric symptoms and complications of therapy were recognized. The overall clinical severity and the progression of the disease in patients with alpha-synPD did not differ from that of the fPD patients. The alpha-synPD patients presented the illness at a younger age and also had lower prevalence of tremor when compared with the fPD patients.

Age of Onset↗

PubMed2003

Growth of asthmatic children before long-term treatment with inhaled corticosteroids.

The aim of this study was to examine the growth of asthmatic children before any long-term inhaled corticosteroid treatment. We studied 436 asthmatic children (254 boys and 182 girls), age range 3.9-15.4 years, that had not been treated with long-term inhaled corticosteroids. In each child height and weight were measured, and the height standard deviation score (HSDS) and the weight for height ratio (%WFH) were calculated. We also estimated asthma severity and tested atopic status by skin testing. Children were grouped into three age groups: prepuberty (3.9-7.9 years), peripuberty (8-11.9 years), and puberty (12-15.5 years). HSDS was correlated to asthma severity and duration, atopic status, and other coexisting allergic diseases. Seven hundred ten healthy children (345 boys, 365 girls) ages 4.1-15.5 years were used as controls for height and weight. There was no statistically significant difference in HSDS and %WFH between patients and controls, except for HSDS of pubertal female patients that was significantly less than that of controls, x: 0.06 (0.80) vs. x: 0.40 (0.90), respectively, p < 0.02. There was also no significant correlation between HSDS or %WFH and severity or duration of the disease, allergy status and other coexisting allergic diseases. However, there was significant difference in menarcheal age between asthmatic girls x: 12.49 (0.12) and controls x: 12.00 (0.10), p < 0.001. In conclusion, our data show that the growth of asthmatic children before any long-term treatment with inhaled corticosteroids is not different from the control population, except for the asthmatic girls of pubertal age who are shorter than control girls probably because of delay in pubertal maturation.

Administration, Inhalation↗

PubMed2002

Nutritional implications of chronic dyspepsia in childhood.

Chronic dyspepsia is common in children. However, the association of individual predominant symptoms with gastric emptying and their impact on nutritional status are poorly defined. We therefore studied 31 children (mean age 11 years, 14 boys) with chronic dyspepsia and classified their predominant symptoms (PS) by their character and severity. Gastric emptying (GE) T(1/2) of a solid meal was carried out in all patients, while upper gastrointestinal endoscopy was done in the treatment failures. All patients received two months treatment with cisapride. Weight for age z scores were recorded before and three months after treatment. There were 12 patients with epigastric pain (EP) as the PS (7 moderate/severe). Postprandial fullness (PF) was the PS in 19 patients (12 moderate/severe). GE T(1/2) was prolonged and weight for age z scores were lower in children who had moderate/severe (but not mild) PF comparing to those who had EP (P < 0.0001 and P = 0.003, respectively). A significant improvement in weight was observed in the same group alone following treatment with cisapride (P = 0.0003). In conclusion, impaired GE is common in dyspeptic children with PF and have adverse effects on nutritional status.

Body Weight↗

PubMed2001

A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family.

Autosomal dominant progressive external ophthalmoplegia (adPEO) is caused by mutations in at least three different genes: ANT1 (chromosome 4q34-35), TWINKLE, and POLG. The ANT1 gene encodes the adenine nucleotide translocator-1 (ANT1). We identified a heterozygous T293C mutation of the ANT1 gene in a Greek family with adPEO. The resulting leucine to proline substitution likely modifies the secondary structure of the ANT1 protein. ANT1 gene mutations may account for adPEO in families with different ethnic backgrounds.

Adenine Nucleotide Translocator 1↗

PubMed2001

The effects of Tween 20 and sucrose on the stability of anti-L-selectin during lyophilization and reconstitution.

We have chosen an anti-L-selectin antibody as a model protein to investigate the effects of sucrose and/or Tween 20 on protein stability during lyophilization and reconstitution. Native anti-L-selectin secondary structure is substantially retained during lyophilization in the presence of sucrose (1 or 0.125%). However, aggregation of the protein during reconstitution of lyophilized protein powders prepared without sucrose is not reduced by the presence of sucrose in the reconstitution medium. Aggregate formation upon reconstitution is completely inhibited by freeze drying the protein with sucrose and reconstituting with a 0.1% Tween 20 solution. Tween 20 (0.1%) also partially inhibits loss of native anti-L-selectin secondary structure during lyophilization. However, upon reconstitution the formulations lyophilized with Tween 20 contain the highest levels of aggregates. The presence of Tween in only the reconstitution solution appears to inhibit the transition from dimers to higher order oligomers. Potential mechanism(s) for the Tween 20 effects were investigated. However, no evidence of thermodynamic stabilization of anti-L-selectin conformation (e.g., by Tween 20 binding) could be detected.

Antibodies, Monoclonal↗

PubMed2001

Clinical features of parkinsonian patients with the alpha-synuclein (G209A) mutation.

The motor and neuropsychological abnormalities in eight Greek patients with Parkinson's disease (PD) carrying the alpha-synuclein gene mutation (G209A) were studied. These patients (five men, three women) belonged to six different families. Their symptoms started between 32-50 years of age (mean +/- SD, 39.7 +/- 7.6 years) and they had a mean disease duration of 5.4 +/- 2.1 years (range, 2-9 years) at the time of examination. Rigidity and bradykinesia predominated both at disease onset as well as in the later stages and rest tremor was relatively uncommon. Neuropsychological assessment showed that one patient was mildly demented while another had impairment in memory, visuoconstructive abilities, and executive function. Depression was present in only one patient. Our findings indicate that genetic forms of parkinsonism share common motor and cognitive characteristics with sporadic PD but raise the possibility that greater cognitive impairment and the relative rarity of tremor may be distinctive features worthy of further investigation.

Adult↗

PubMed2001

Retrospective study of a large population of patients affected with mitochondrial disorders: clinical, morphological and molecular genetic evaluation.

Mitochondrial disorders are human genetic diseases with extremely variable clinical and genetic features. To better define them, we made a genotype-phenotype correlation in a series of 207 affected patients, and we examined most of them with six laboratory examinations (serum CK and basal lactate levels, EMG, cardiac and EEG studies, neuroradiology). We found that, depending on the genetic abnormality, hyperckemia occurs most often with either chronic progressive external ophthalmoplegia (CPEO) and ptosis or with limb weakness. Myopathic EMGs are more common than limb weakness, except in patients with A8344G mutations. Peripheral neuropathy, when present, is always axonal. About 80% of patients with A3243G and A8344G mutations have high basal lactate levels, whereas pure CPEO is never associated with increased lactate levels. Cardiac abnormalities mostly consist of conduction defects. Abnormalities on CT or MRI of the brain are relatively common in A3243G mutations independently of the clinical phenotype. Patients with multiple mtDNA deletions are somehow "protected" against the development of abnormalities with any of the tests. We conclude that, despite the phenotypic heterogeneity of mitochondrial disorders, correlation of clinical features and laboratory findings may give the clinician important clues to the genetic defect, allowing earlier diagnosis and counselling.

Adolescent↗

PubMed2001

Spinal cord compression due to extramedullary haematopoiesis in two patients with thalassaemia: complete regression with blood transfusion therapy.

Extramedullary haematopoiesis, a common finding in thalassaemia, is rarely localized in the spinal cord and even more rarely has neurological manifestations. We present two patients suffering from thalassaemia (intermedia and beta homozygous) and paraparesis due to spinal cord compression from intrathoracic extramedullary haematopoietic masses. Diagnosis was based on magnetic resonance imaging findings, and treatment consisted of blood hypertransfusions. The majority of published cases have been successfully treated by radiation and in some cases by blood transfusions. Our two patients completely recovered, and there has been no recurrence during the 4 years since their treatment. Diagnosis and treatment of this rare condition are discussed.

Adult↗

PubMed2001

A new homogeneous enzyme immunoassay for thyroxine using glycogen phosphorylase b-thyroxine conjugates.

BACKGROUND: [corrected] Measurement of serum thyroxine (T(4)) concentration is important for diagnosis of thyroid gland diseases. We developed a practical homogeneous enzyme immunoassay for thyroxine analysis in unextracted sera. METHODS: A thyroxine derivative conjugated to a reactive sulfhydryl group of glycogen phosphorylase b (GPb). Conjugation caused inhibition of enzyme activity and the enzyme conjugate was re-activated upon the binding of a polyclonal anti-T(4) antibody. Antibody-activation was blocked by the presence of free T(4). RESULTS: Conjugation affected the allosteric character of the enzyme and the K(m) for the allosteric activator AMP was increased 28 times, while anti-T(4) antibody partially reversed this effect. The optimum concentration ratio of enzyme conjugate to anti-T(4) antibody was determined, and T(4) was measured with desired sensitivity and accuracy in the range between 10 and 240 microg/l. Furosemide was used to inhibit the interaction of thyroxine with serum T(4)-binding sites. Human serum T(4) values obtained by this method correlated well with those obtained by a radioimmunoassay (y=1.9+1.0x, r=0.97, N=72). CONCLUSIONS: Chemical modification of glycogen phosphorylase b with a T(4) derivative led to the development of a simple homogenous enzyme immunoassay for T(4) analysis with the desired sensitivity and accuracy.

Allosteric Regulation↗

PubMed2001

Hypercalciuria in children with febrile convulsions.

BACKGROUND: The purpose of the present study was to investigate whether idiopathic hypercalciuria may be implicated in the pathogenesis of febrile convulsions. METHODS: We studied 38 children (22 boys) with febrile convulsions (mean (+/- SD) age 3.25 +/- 1.09 years) and 45 healthy children (28 boys) of similar age who served as controls. Twenty-four hour urine calcium and phosphate, as well as serum calcium, phosphate, alkaline phosphatase and intact parathyroid hormone (PTH) concentrations were determined. RESULTS: Hypercalciuria (urine Ca >4.0 mg/kg bodyweight per 24 h) was found in nine children with febrile convulsions (23.7%) and in three controls (6.7%). Hypercalciuric children excreted significantly more phosphate in their urine (37.0 +/- 11.6 mg/kg bodyweight per 24 h) than normocalciuric children (18.7 +/- 8.7 mg/kg bodyweight per 24 h) and controls (20.2 +/- 7.6 mg/kg bodyweight per 24 h). They also had higher serum intact PTH concentrations (49.87 +/- 15.36 pg/mL) than normocalciuric (35.39 +/- 15.67 pg/mL) and control children (28.21 +/- 14.00 pg/mL). According to the calcium-loading test, eight of nine children with hypercalciuria had the renal type of the disorder. Furthermore, hypercalciuric children had significantly more convulsive episodes (2.77 +/- 1.98) than normocalciuric children (1.86 +/- 1.24). CONCLUSIONS: Our results suggest that renal hypercalciuria may be implicated in the pathogenesis of febrile convulsions.

Calcium↗

PubMed2001

Clinical phenotype in patients with alpha-synuclein Parkinson's disease living in Greece in comparison with patients with sporadic Parkinson's disease.

OBJECTIVE: An Ala53Thr mutation of the alpha-synuclein gene has been recently identified as a rare cause of autosomal Parkinson's disease (PD). The clinical characteristics of 15 patients with PD living in Greece with the Ala53Thr alpha-synuclein mutation (alpha-synPD) were compared with patients with sporadic Parkinson's disease (sPD). METHODS: An investigator, blind to the results of the genetic analysis, examined 15 patients with alpha-synPD and 52 consecutive patients with sPD. Demographic data, age at onset of the illness, modality of presentation, and duration of PD were collected. The unified Parkinson's disease rating scale, the Hoehn and Yahr scale, and the Schwab-England scale were completed. The patients with alpha-synPD were matched for duration of disease with 32 of the 52 patients with sporadic PD (MsPD group). RESULTS: Patients with the alpha-synuclein mutation were significantly younger (mean 7.6 years), showed the first sign of the disease significantly earlier in life (mean 10.8 years), and had significantly longer duration of the disease compared with patients with sPD. Tremor at onset of the disease was present in only one (6.7%) of the patients with alpha-synPD, whereas it was present in 32 (61.5%) of the patients with sPD (p=0.0006). During the course of the disease one patient in the alpha-synPD group went on to develop tremor compared with six patients in the sPD group. Rigidity, bradykinesia, postural instability, orthostatic hypotension, intellectual impairment, depression, complications of therapy, and clinical severity of the disease at the time of examination did not differ significantly between patients with alpha-synPD and those with sPD, or between patients with alpha-synPD and the MsPD group. CONCLUSION: The younger age at onset of the illness, the much lower prevalence of tremor, and the longer duration of the disease characterise the clinical phenotype in this sample of patients with alpha-synPD. The other symptoms and signs of the illness did not seem to differentiate the patients with alpha-synPD from those with sPD.

Adult↗

PubMed2001

The anabolic steroid oxandrolone increases muscle mass in prepubertal boys with constitutional delay of growth.

The aim of this study was to investigate the effect of oxandrolone on body composition in boys with constitutional delay of growth and puberty. In 14 prepubertal boys, height, weight, triceps and subscapular skinfolds and upper arm circumference were measured. Body mass index, the ratio of subscapular to triceps skinfolds and the upper muscle area were also determined. The difference of the various measurements and indices, 3 to 6 months before and after commencement of oxandrolone treatment, were calculated, while the boys remained prepubertal. We observed a marked increase in body mass index, a decrease of triceps and subscapular skinfolds, an increase in the ratio of subscapular to triceps skinfolds and also an increase in upper muscle area after the onset of oxandrolone treatment. These results suggest that low dose oxandrolone administration in prepubertal boys with constitutional growth delay causes a disproportionate increase of weight to height which is largely due to increased body muscle.

Anabolic Agents↗

PubMed2001

Sex differences in the secular changes in pubertal maturation.

OBJECTIVE: It is a common experience among pediatricians in the industrialized countries that many girls-but many fewer boys-present with secondary sex characteristics at a younger age than normal. This study examines whether there are sex differences in the secular changes toward earlier pubertal maturation. METHODS: The author collected the growth data from various studies performed in Greece in the 20th century (from 1928 to 1995) and estimated the age at peak annual height increment in each study by calculating mean increase in height in each successive year. RESULTS: In all studies, boys presented peak mean annual height increment at 13 to 14 years of age. Girls did not present a discernible peak height increment until the late 1960s; however, thereafter they presented a peak height increment at 11 to 12 years of age. CONCLUSIONS: The data suggest sex differences in the secular changes in pubertal maturation, girls being affected more intensely than boys.

Adolescent↗

PubMed2001

Homogeneous enzyme immunoassay for triiodothyronine in serum.

BACKGROUND: The concentration of triiodothyronine (T3) in human serum is extremely low and can be determined only by very sensitive methods. We developed a homogeneous enzyme immunoassay for T3 analysis in unextracted serum. METHODS: A T(3) derivative was conjugated to the -SH groups of glycogen phosphorylase b (GPb) from rabbit muscle. Conjugation caused inhibition of enzyme activity, and the enzyme conjugate was reactivated upon binding of anti-T3 antibody. Activation was blocked by the presence of non-antibody-bound T3; this was the basis for the development of the homogeneous enzyme immunoassay for T3 by determining GPb activity fluorometrically. RESULTS: We used furosemide to block the interaction of T3 with serum proteins with T3-binding sites, avoiding any serum treatment step. T3 was measured in the range 0.3-8 microg/L. T3 values obtained by this assay correlated well with those obtained by a RIA (y = 0.97x - 0.07 microg/L; r = 0.96; n = 92). Within- and between-run imprecision (CV) was 5-9% for normal and high concentrations and 16-20% for low concentrations. CONCLUSIONS: Chemical modification of GPb with a T3 derivative allows the development of a simple homogeneous enzyme immunoassay for T3 in unextracted serum.

Adult↗

PubMed2000

Recombinant antibody toxins specific for ErbB2 and EGF receptor inhibit the in vitro growth of human head and neck cancer cells and cause rapid tumor regression in vivo.

Overexpression of the ErbB2 and epidermal growth factor receptor (EGFR) tyrosine kinases is frequently observed in squamous cell carcinomas of the head and neck, and has been correlated with shorter overall survival. By immunoblot analysis, we have found EGFR and ErbB2 expression in 6 out of 6 established head and neck cancer cell lines. Elevated EGFR protein levels were noted in 3 and elevated ErbB2 levels in 5 of them. Significant expression of EGFR and ErbB2 was also detected in 17 of 47 and 26 of 45 primary tumor samples. Due to their enhanced expression on the tumor cell surface, these receptors can be regarded as suitable targets for directed cancer therapy. We have analyzed the antitumoral activity of recombinant single-chain antibody toxins specific for ErbB2 and EGFR against head and neck cancer cells in vitro and in vivo. The recombinant toxins consist of the variable domains of the heavy and light chains of monoclonal antibodies (MAbs) genetically fused to a truncated Pseudomonas exotoxin A (ETA). At low concentrations, the ErbB2-specific single-chain antibody (scFv) toxin scFv(FRP5)-ETA and the EGFR-specific toxins scFv(225)-ETA and scFv(14E1)-ETA inhibited the in vitro growth of established head and neck cancer cell lines and primary tumor cells. In a nude mouse tumor model, intratumoral injection of the antibody toxins resulted in the rapid regression of subcutaneously growing CAL 27 tumor xenografts, with scFv(FRP5)-ETA and scFv(14E1)-ETA treatment being most effective and leading to the cure of up to 50% of the animals. Our results suggest that EGFR and ErbB2-specific antibody toxins may become valuable therapeutic reagents for the treatment of squamous cell carcinomas of the head and neck.

ADP Ribose Transferases↗

PubMed2000

Atrial natriuretic peptide in children with idiopathic hypercalciuria.

We measured plasma atrial natriuretic peptide (ANP) levels in 30 children with idiopathic hypercalciuria (IH) and 19 normal controls (NC). A calcium (Ca) loading test was performed in all patients to determine the type of IH. Subsequently plasma ANP, cAMP and renin activity (PRA), serum total and ionized Ca, intact parathyroid hormone, aldosterone, and 1,25-dihydroxyvitamin D as well as urine Ca, cAMP, and electrolytes were determined in all subjects. The mean (SD) plasma ANP levels were significantly lower in patients with renal hypercalciuria (RH) [21.4 (4.8) pg/ml] than in those with absorptive hypercalciuria (AH) [26.8 (7.6) pg/ml, P<0.05] and NC [27.6 (6.6) pg/ml, P<0.001]. PRA was significantly lower in AH [2.9 (1.3) ng/ml per hour] than in RH patients [7.8 (6.8) ng/ml per hour, P<0.01] and in NC [6.8 (4.6) ng/ml per hour, P<0.005]. Serum aldosterone values were significantly lower in AH [14.5 (11.4) ng/dl] than in RH patients [25.4 (14.1) ng/dl, P<0.05] and in NC [32.6 (20.5), P<0.001]. The lower plasma ANP levels in RH than in AH patients and in NC may be due to Ca depletion. The lower PRA and serum aldosterone levels in AH than in RH patients and in NC may be attributed to Ca excess.

Aldosterone↗

PubMed2000

Stiff-person like syndrome in a patient with multiple pituitary hormone deficiencies.

A patient with long-standing, occult pituitary insufficiency, who developed painful muscle stiffness and superimposed spasms, closely resembling stiff-person syndrome, was described. Complete resolution of neuromuscular symptoms with hormone replacement in this case, as well as in a previously reported one, led to the suggestion that a syndrome like stiff-person could represent a rare consequence of multiple pituitary hormone deficiencies.

Female↗

PubMed2000

Plasma immunoreactive endothelin levels in children with cystic fibrosis.

UNLABELLED: Plasma immunoreactive endothelin levels were determined in 31 children and adolescents with cystic fibrosis and it was examined whether these levels correlated with the severity of the disease. The study comprised 16 cystic fibrosis patients (mean (SD) age 13.0 (4.9) y) with impaired lung function (Group A), 15 cystic fibrosis patients (11.2 (5.5) y) with unimpaired lung function (Group B) and 28 healthy controls (10.6 (4.3) y) (Group C). The selection and classification of patients into groups was based on criteria including the grade of finger-clubbing, the Brasfield chest radiograph score and spirometric and arterial blood gas values. In all subjects, plasma immunoreactive endothelin, atrial natriuretic peptide, renin, serum aldosterone levels and serum and urine electrolytes were measured. CONCLUSIONS: Plasma endothelin levels were significantly higher in Group A (range 2.5-8.4 pg/ml, median 3.2 pg/ml) than those in Group B (1.3-3.8 pg/ml, median 2.0 pg/ml, p < 0.001) and Group C (1.5-3.5 pg/ml, median 2.5 pg/ml, p < 0.001), whereas they did not differ between groups B and C. They correlated positively with the severity of finger-clubbing, heart rate, arterial blood PCO2, plasma atrial natriuretic peptide levels and serum aldosterone levels and negatively with the arterial blood PO2, forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and the Brasfield chest radiograph score. In multivariate regression analysis PO2 was the only independent factor found to significantly affect plasma endothelin levels. In conclusion, plasma immunoreactive endothelin levels are increased in cystic fibrosis patients with impaired pulmonary function and are related to the severity of the disease.

Adolescent↗