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Biomedical subjects

C Christodoulou

Publications and source records attributed to C Christodoulou.

At least 55 records · Page 3Linked to original sources
PubMed2000

Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study.

PURPOSE: To evaluate the efficacy of the carboplatin/paclitaxel combination in patients with carcinoma of unknown primary site (CUP). PATIENTS AND METHODS: Seventy-seven consecutive CUP patients (45 women and 32 men; median age, 60 years) were treated with carboplatin at target area under the curve 6 mg/mL/min followed by paclitaxel 200 mg/m(2) as a 3-hour infusion and granulocyte colony-stimulating factor from days 5 to 12. Treatment courses were repeated every 3 weeks to a maximum of eight cycles. Forty-seven patients had adenocarcinomas, 27 had undifferentiated carcinomas, and three had squamous cell carcinomas. Thirty-three patients presented with liver, bone, or multiple organ metastases, 23 with predominantly nodal/pleural disease, and 19 (16 women) with peritoneal carcinomatosis. RESULTS: The overall response rate by intent-to-treat analysis was 38.7% (95% confidence interval, 27.5% to 49.9%). There were no differences in response between adenocarcinomas and undifferentiated carcinomas, but efficacy varied among clinical subsets. The response rates and median survival times in the three clinically defined subsets were 47.8% and 13 months, respectively, for patients with predominantly nodal/pleural disease, 68.4% and 15 months, respectively, in women with peritoneal carcinomatosis, and 15.1% and 10 months, respectively, in patients with visceral or disseminated metastases. Chemotherapy was well-tolerated. CONCLUSION: Carboplatin plus paclitaxel combination chemotherapy is effective in patients with predominantly nodal/pleural metastases of unknown primary carcinoma and in women with peritoneal carcinomatosis. However, in patients with liver, bone, or multiple organ involvement, the combination offers limited benefit. The investigation of novel treatment approaches is highly warranted for this group of patients.

Adenocarcinoma↗
PubMed1999

Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine.

Galactose-targeted delivery of macromolecules and drug conjugates to asialoglycoprotein receptor (ASGPR) positive cells has been widely documented in animals, although targeting in humans has never been demonstrated. In this study we report the pharmacokinetics and imaging determined in the first patient enrolled in a phase I clinical study of the poly[N-(2-hydroxypropyl)methacrylamide] copolymer bearing doxorubicin and galactosamine, known as PK2. Gradient high performance liquid chromatography (HPLC) evaluation of plasma and urine has been combined with 123I-based imaging to show biphasic clearance of the drug from the plasma (half-lives of 78+/-1 and 990+/-15), and approximately 30% delivery of the drug to the hepatic region, as determined by planar whole body imaging at 24 h. This patient has a multifocal hepatoma, and single photon emission computed tomography (SPECT) analysis showed a ratio of tumour tissue to normal liver uptake of approximately 1:3, at 24 h. On the basis of this patient, effective hepatic targeting can be achieved following an intravenous dose of 20 mg/m2 doxorubicin as PK2, however the therapeutic usefulness of this targeted drug has yet to be established.

Antibiotics, Antineoplastic↗
PubMed1999

Examination of Cloninger's basic dimensions of personality in fatiguing illness: chronic fatigue syndrome and multiple sclerosis.

Relatively few studies have examined the personality characteristics of patients with chronic fatigue syndrome (CFS). The personality profiles of 38 CFS subjects were compared with 40 healthy controls and 40 subjects with multiple sclerosis (MS), a chronic illness that shares many symptoms with CFS (e.g., fatigue), but has a known neurological substrate. Subjects were examined within Cloninger's biosocial theory of personality, which delineates basic dimensions of temperament. Both illness groups displayed similarly elevated levels of Harm Avoidance, and lower levels of Reward Dependence as compared with healthy controls. The MS group showed a lower level of Persistence than controls and CFS subjects. Implications for the relationship between chronic illness and personality are discussed.

Adult↗
PubMed1999

Prevalence of antibodies to hepatitis A among children and adolescents in Larnaca area, Cyprus.

The prevalence of antibodies to hepatitis A virus was investigated in 385 children and adolescents (52.2% males), aged 6 to 18, in the Larnaca area of Cyprus. This is the first study investigating the prevalence of hepatitis A in Cyprus for this age group. The population was stratified into two groups: 6 to 12 years old and 13 to 18 years old. None of the subjects in the first group were positive. The prevalence of hepatitis A in the age of group 13 tol8 was 1.6%. In conclusion, the low prevalence of anti-HAV demonstrates the susceptibility of young Cypriots to hepatitis A. This is a cause for concern as these unprotected young adults are frequently exposed to potentially infected individuals.

Adolescent↗
PubMed1998

Asymptomatic bacteriuria in puppies with canine parvovirus infection: a cohort study.

This study aimed to investigate the possible association between canine parvoviral enteritis and asymptomatic bacteriuria. Forty-three puppies that were admitted to the outpatient service of the Animal Medical Clinic with clinical signs compatible with parvoviral enteritis formed the exposed group. The clinical diagnosis was subsequently confirmed by a positive fecal ELISA test (CITE test: IDDEX Lab., Westbrook, ME). Twenty-three (53.5%) of these puppies were males and 20 (46.5%) were females. Their age ranged from 1.5 to 5.5 months. Forty-eight clinically normal and age-matched puppies, that had been admitted to the clinic for vaccinations and had a negative result in the aforementioned ELISA test, were randomly selected to form the unexposed group. Urine samples were collected by antebupic cystocentesis from all puppies and submitted for bacterial culture. In the parvovirus exposed group, 11 of 43 puppies had detectable bacteriuria. The isolates were Escherichia coli alone (8/11-72.7%) Staphylococcus aureus alone (1/11-9.1%) and mixed cultures of E. coli and S. epidermitis (2/11-18.2%). In the unexposed group there were three puppies with detectable bacteriuria, one isolate each of E. coli, Enterococcus durans and Corynebacterium spp. Puppies with parvoviral enteritis had five (95% CI: 1.3-19.8) times higher odds of developing asymptomatic bacteriuria than puppies without the disease. The observed increased risk of asymptomatic bacteriuria among puppies with parvoviral enteritis was probably due to the fecal contamination of the external genitalia and the neutropenia these puppies exhibited.

Animals↗
PubMed1998

Acquisition and storage deficits in multiple sclerosis.

This study examined whether verbal and visual memory impairments in multiple sclerosis (MS) are attributable to deficits in acquisition, storage, or retrieval. Volunteers with MS (n = 40) and healthy controls (n = 20) rehearsed a word list and a checkerboard pattern using a selective reminding procedure until two consecutive error-free trials were attained. Recall and recognition were assessed after 30 min and 90 min (and 1 week for verbal material) delays. The MS group required significantly more trials to attain criterion on both learning tests. Once equated for acquisition, both groups performed similarly on verbal recall and recognition. However the MS group performed significantly worse on measures of visual recall and recognition. The results suggest that the verbal memory impairment in MS is due to deficient acquisition, while the visual memory impairment in MS is attributable to deficits in acquisition and storage.

Adult↗
PubMed1998

Immunoglobulin double isotype-producing hybridomas isolated from an autoimmune (NZB x NZW)F1 mouse.

In the sera of (NZB x NZW)F1 (B/W) mice that develop a lupus-like syndrome, increased levels of IgG antibodies (Ab) reacting with TNP have been detected before the appearance of IgG anti-DNA Ab and clinical symptoms. A single injection of trinitrophenyl-bovine serum albumin (TNP/BSA) in physiological saline into a young B/W mouse (3 months old), followed by fusion of its splenocytes 3 days later, gave rise to hybridomas simultaneously secreting IgM and IgG Ab with anti-TNP reactivity. Both mu and gamma chains were detected in culture supernatants by ELISA, and double isotype-producing cells were labeled by immunofluorescence. Molecular analysis of two of these double isotype-producing hybridomas showed the presence of mRNA coding for both mu and gamma chains of Ig, and this gamma mRNA could be translated in vitro into a gamma heavy (H) chain. Comparison of the H chain variable-region sequences of IgM and IgG revealed 100% homology between mu and gamma V(H) genes in one clone, while mu and gamma V(H) genes showed only 80% homology in the other clone. Both clones produced a single kappa light (L) chain. These two hybridomas, isolated from a B/W mouse, thus represent two different mechanisms of double isotype expression: the first one corresponds to an IgM to IgG switch, while the second one reflects a lack of allelic exclusion.

Alleles↗
PubMed1998

Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome.

OBJECTIVES: To examine the relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome, and determine whether the relation is independent of psychiatric factors. METHODS: The subjects were 53 patients with chronic fatigue syndrome and 32 healthy controls who did not exercise regularly. Subjects were administered a structured psychiatric interview and completed questionnaires focusing on depression and functional disability. They also completed a battery of standardised neuropsychological tasks focusing on the cognitive domains that patients with chronic fatigue syndrome experience as particularly difficult: memory (verbal and visual), and attention/concentration. A test score was defined as failing when it was > or =2 SD below the mean of the healthy controls after controlling for demographic factors. RESULTS: Those patients with chronic fatigue syndrome with higher numbers of failing neuropsychological test scores reported significantly more days of general inactivity in the past month than those with fewer failing scores. This result remained significant even after partialling out the contribution of the presence of a comorbid axis I psychiatric episode and the overall level of depressive symptomology. Patients with failing verbal memory scores were particularly functionally disabled compared with those with passing scores. CONCLUSION: A relation was found between cognitive impairment and functional disability which could not be explained entirely on the basis of psychiatric factors.

Activities of Daily Living↗
PubMed1997

Chemotherapy with methotrexate, vinblastine, epirubicin and carboplatin (Carbo-MVE) in transitional cell urothelial cancer. A Hellenic Co-Operative Oncology Group study.

OBJECTIVES: We conducted a phase II study in order to assess the efficacy and toxicity of Carbo-MVE (carboplatin 250 mg/m2 i.v. day 1, methotrexate 25 mg/m2 i.v. days 1, 15 and 22, vinblastine 2.5 mg/m2 i.v. days 1, 15 and 22 and epirubicin 25 mg/m2 day 1). The regimen ws to be repeated every 28 days. METHODS: Forty-six patients with transitional cell carcinoma of the bladder entered the study. Patients with metastatic disease were treated for 6 cycles, while patients with locally advanced or locoregional disease had 4 cycles of induction chemotherapy followed by cystectomy or radiotherapy. RESULTS: Toxicity was generally mild and treatment well tolerated. The overall response rate was 54.4%, with 26% complete and 28.3% partial response rates. The median survival was 17.5 months with the complete responders to live significantly longer (64.82 months) than those who had a partial response (20.5 months), stable disease (15 months) or progressive disease (8.5 months). Survival was also significantly longer in patients with good performance status as well as in patients with locally advanced or locoregional disease. Finally, patients who had cystectomy as definitive treatment survived significantly longer (32 months) than those who had been irradiated (16 months). CONCLUSIONS: The Carbo-MVE regimen appears to be an effective and well-tolerated treatment in patients with transitional cell carcinoma of the bladder.

Aged↗
PubMed1996

Conservation of synteny between the genome of the pufferfish (Fugu rubripes) and the region on human chromosome 14 (14q24.3) associated with familial Alzheimer disease (AD3 locus)

The genome of the pufferfish (Fugu rubripes) (400 Mb) is approximately 7.5 times smaller than the human genome, but it has a similar gene repertoire to that of man. If regions of the two genomes exhibited conservation of gene order (i.e., were syntenic), it should be possible to reduce dramatically the effort required for identification of candidate genes in human disease loci by sequencing syntenic regions of the compact Fugu genome. We have demonstrated that three genes (dihydrolipoamide succinyltransferase, S31iii125, and S20i15), which are linked to FOS in the familial Alzheimer disease focus (AD3) on human chromosome 14, have homologues in the Fugu genome adjacent to Fugu cFOS. The relative gene order of cFOS, S31iii125, and S20i15 was the same in both genomes, but in Fugu these three genes lay within a 12.4-kb region, compared to >600 kb in the human AD3 locus. These results demonstrate the conservation of synteny between the genomes of Fugu and man and highlight the utility of this approach for sequence-based identification of genes in human disease loci.

Acyltransferases↗
PubMed1996

Streptococcus agalactiae: a vaginal pathogen?

The significance of Streptococcus agalactiae as an aetiological agent in vaginitis was evaluated. A total of 6226 samples from women who presented with vaginal symptoms was examined. The presence of >10 leucocytes/high-power field (h.p.f.) was taken to be the criterion of active infection. S. agalactiae was isolated from 10.1% of these samples. The isolation rates of other common pathogens such as Candida spp., Gardnerella vaginalis and Trichomonas spp. were 54.1%, 27.2% and 4.2%, respectively, in the same group of patients. In contrast, the isolation rates of these micro-organisms in the group of patients who had no infection (<10 leucocytes/h.p.f.) were 4.2%, 38.3%, 33% and 0.5%, respectively. In the majority of samples from which S. agalactiae was isolated, it was the sole pathogen isolated (83%) and its presence was associated with an inflammatory response in 80% of patients. Furthermore, the relative risk of vaginal infection with S. agalactiae (2.38) in patients with purulent vaginal discharge was greater than that of Candida spp. infection (1.41) and lower than that of Trichomonas spp. infection (8.32). These data suggest that S. agalactiae in symptomatic women with microscopic evidence of inflammation should be considered a causative agent of vaginitis.

Adolescent↗
PubMed1995

Bacterial secretion of the Fab fragment of a mouse monoclonal IgM that reacts with IgG variable regions.

In this report, we describe the expression system that enabled us to produce in Escherichia coli the Fab fragment of a mouse IgM that has previously been shown to inhibit the binding of IgG to autoantigens by interacting with their variable regions. In our system, both light chain and heavy chain fragments were put under the control of the malE promoter. The light chain was fused to the MalE signal sequence, while the heavy chain variable and first constant region were fused to the alkaline phosphatase signal sequence. In this system, after induction of the promoter with maltose, the Fab fragment could be detected in a periplasmic extract of the bacteria by Western blotting and also by ELISA. This Fab fragment was purified on a goat anti-mouse immunoglobulin immunoadsorbent and biotinylated. The Fab fragment produced by E.coli reacted with the trinitrophenyl (TNP) hapten and F(ab')2 fragments of mouse IgG and these reactivities could be specifically inhibited by the corresponding soluble antigens. The dissociation constants of this Fab were 1.65 x 10(-6) M for TNP and 5 x 10(-6) M for IgG F(ab')2 fragments, indicating that the affinity of the Fab fragment compared with that of the whole IgM molecule was similar for TNP but was lower for IgG F(ab')2 fragments.

Animals↗
PubMed1995

Primary causes of fetal deaths in Athens a clinicopathological study.

The authors studied 239 cases of fetal death, occurring before the 24th week of gestation, during a five-year period, from 1989 to 1993. Based on clinical information and autopsy findings, their cases were classified as follows: 1) amniotic infection syndrome; 2) congenital anomalies; 3) disorders of the placenta and adnexae, and 4) others. The causes of fetal death were determined and evaluated statistically. In 83 cases (39 %), only autopsy revealed the cause of fetal death. The correlation of clinical and pathological findings showed that autopsy constitutes an important source of information for the determination of causes of fetal death, as well as for future genetic counselling. Moreover, it can broaden our knowledge about perinatal mortality, by correctly interpreting clinical and complementary investigation data.

Abortion, Spontaneous↗
PubMed1994

Reactivity and structure of a mouse anti-F(ab')2 IgM. Comparison of its variable region sequences with those of a structurally close polyreactive natural IgM.

IE12 is a monoclonal IgM with strong anti-F(ab')2 activity that inhibits the binding of normal mouse IgG to self antigens. In this study, we found that this IgM was also reactive with several monoclonal antibodies (mAbs), myeloma proteins and B lymphocytes from normal BALB/c mouse. The nucleotide sequences of the variable region of the heavy and light chains of IE12 were determined, and compared to those of another mAb already described in the literature. This mAb uses the same light chain and also the same VH, D and JH segments, but unlike IE12, is polyreactive. The comparison of the amino acid composition of these two mAbs and of the computer predictions for their structure and hydrophilicity indicated that the most striking difference between them was located in the third complementarity determining region (CDR3) of the heavy chain. Indeed, they used the same D segment but translated in two different reading frames, leading to different amino acid compositions. The CDR3 of IE12 contains aliphatic amino acids, while that of the polyreactive IgM does not. In addition, IE12 has two prolines, one at each at each extremity of its D segment, that could confer a certain rigidity to this region. Finally, the CDR3 of IE12 is predicted to be hydrophobic, while the one of the polyreactive IgM is predicted to be hydrophilic and more flexible, suggesting that the hydrophilicity and the flexibility of this region might be critical for polyreactivity.

Amino Acid Sequence↗