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Biomedical subjects

M Papadakis

Publications and source records attributed to M Papadakis.

At least 19 recordsLinked to original sources

Polymyositis in a patient with recurring ovarian cancer and history of unrelated breast cancer.

BACKGROUND: Polymyositis (PM) is an idiopathic inflammatory myopathy. Occasionally, it may present as a paraneoplastic syndrome and it is strongly associated with ovarian and weakly with breast cancer. We present here a case of a 60-year-old patient with sequential breast and ovarian (second primary) carcinomas followed by PM as a paraneoplastic disorder. CASE REPORT: The patient had been diagnosed with stage I breast carcinoma 3 years ago and had been treated with conservative surgery followed by radiotherapy and six cycles of chemotherapy (CMF). One and a half year later an ovarian carcinoma was diagnosed for which the patient underwent abdominal hysterectomy oophorectomy and omentectomy. The pathological report characterized it as second primary. Adjuvant chemotherapy with carboplatin and taxol was administered. Fourteen months after the initial laparotomy, the patient was re-operated due to ovarian carcinoma recurrence which was involving all lesser pelvis organs. After a successful radical removal of the recurrence the patient developed a fully expressed PM. This case serves to remind that this disease can occur as a paraneoplastic disorder.

Adenocarcinoma↗

Neuroprotection and neurogenesis: modulation of cornus ammonis 1 neuronal survival after transient forebrain ischemia by prior fimbria-fornix deafferentation.

Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Temperature was regulated and rats survived for 7, 14 or 28 days. Immunofluorescent bromodeoxyuridine and neuron specific nuclear protein staining and immunochemistry terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining were performed. At 7 days after ischemia, 73%+/-14% of cornus ammonis 1 neurons were damaged, while deafferentation reduced the injury to 36%+/-17% of cornus ammonis 1 neurons. This protection persisted for at least 28 days. Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.

Analysis of Variance↗

Translational vehicles for neuroprotection.

This review will analyse particular criteria in the analysis of stroke diagnosis and treatment, which are pivotal for the successful translation of experimental data from the laboratory to humans.

Animals↗

Standardized patients' perceptions about their own health care.

BACKGROUND: There have been detailed descriptions on standardized patients (SP) programs' effects on students, curricula, and faculty, yet little attention has been paid to the consequences of participating on the SP's. PURPOSE: This study explored the perceptions of SPs toward their own health care in the context of having served as SPs. METHOD: All 180 SPs participating in Department of Medicine programs at 5 medical schools were surveyed. They completed the survey during SP activities, or it was mailed to them. SPs indicated their level of agreement or disagreement with 11 attitude statements related to their own health care after serving as an SP using a Likert scale, with 1 reflecting the most positive attitude and 5 the least positive. RESULTS: Responses to the attitudinal questions were obtained from 164 SPs (91%). SPs perceived that because of their participation as SPs they had a better understanding about medical history taking and physical examinations (1.9 +/- 0.9), communicated more effectively with their health care provider (1.8 +/- 0.9), and were more comfortable with both health care visits and physical examinations (2.2 +/- 0.9). There were no significant differences in results based on gender, age, race, or school. CONCLUSIONS: As a consequence of their participation, the SPs indicated a change in attitudes about their personal health care. They perceived improved understanding and ability to communicate and comfort with their own health care. Participation in SP programs seems to influence SPs by improving perceptions about their own health care interactions.

Adolescent↗

Combination chemotherapy with docetaxel, vinorelbine and cisplatin as first-line treatment of advanced non-small-cell lung cancer: a multicenter phase II study of the Greek Cooperative Group for Lung Cancer.

Vinorelbine, docetaxel and cisplatin have documented single-agent activity in non-small-cell lung cancer (NSCLC); a multicenter phase II trial was initiated in order to evaluate the tolerance and efficacy of their combination. A total of 24 chemotherapy-naive patients with measurable stage IIIB or IV NSCLC and performance status (PS; WHO) 0-2 entered the study. Vinorelbine (20 mg/m2 i.v.) was given on days 1 and 15, cisplatin (60 mg/m2) on day 1, and docetaxel (100 mg/m2) on day 16, in cycles of 28 days. Recombinant human granulocyte colony-stimulating factor (150 microg/m2 s.c.) was administered prophylactically from day 17 to day 27. One pathological complete (4%) and six partial responses (25%) were documented (overall response 29%; 95% CI 11.6-49.2%). A total of five patients (21%) had stable and 12 (50%) progressive disease. The median duration of response was 28 weeks and the median time to tumor progression 36 weeks; the median survival was 20 weeks. Grade 3-4 neutropenia occurred in 16 patients (67%) while 13 of them (54%) developed febrile neutropenia. Grade 4 mucositis occurred in two patients (8%) and one of them also presented grade 4 diarrhea. There were four treatment-related deaths: two from sepsis, one from massive hemoptysis due to a pulmonary abscess and one from acute myocardial ischemia 7 days post-chemotherapy. In conclusion, the high incidence of neutropenic episodes and treatment-related deaths led to an early discontinuation of patient enrollment. This combination, in the schedule and the doses used, could not be recommended for off protocol treatment of patients with advanced NSCLC.

Adult↗

delta-Thalassemic phenotype due to two "novel" delta-globin gene mutations: CD11[GTC-->GGC (A8)-HbA2-Pylos] and CD 85[TTT-->TCT(F1)-HbA2-Etolia].

delta-Thalassemia reduces the expected HbA2 percentage, altering the normal as well as the beta-thalassemia trait phenotype. An attempt to elucidate the molecular basis of delta-thalassemia in the Greek population, revealed two cases with unknown molecular defects that presented low levels of HbA2 (about 1.5%). DNA sequence analysis of delta-globin gene identified two "novel" mutations in the coding regions of the gene; the cd11 (GTC-->GGC) resulting in the substitution of valine for glycine (:HbA2-Pylos) and the cd85(TTT-->TCT) resulting in the substitution of phenylalanine for serine (:HbA2-Etolia). Because these mutations are localized at the helical positions A8 and F1 of the HbA2 respectively, they potentially cause molecular instability of the tetramer, thus leading to reduced HbA2 percentage.

Adult↗

Scanning method to identify the molecular heterogeneity of delta-globin gene especially in delta-thalassemias: detection of three novel substitutions in the promoter region of the gene.

A scanning strategy for the detection of delta-globin gene mutations and polymorphisms is presented. This procedure is based on the denaturing gradient gel electrophoresis (DGGE) of four different artificially amplified DNA fragments which cover the promoter, the exons, as well as IVS I of the reported gene. To estimate the efficiency and sensitivity of the proposed procedure, we analysed the appropriate controls of delta-thalassemic carriers, uncharacterised delta-thalassemias and cases with normal hematological phenotype, but slightly increased (up to 3.5%) HbA2. DGGE results permitted the identification of delta-globin gene mutations and the polymorphism -199 (T-->C). Three novel base substitutions inside the promoter region of the gene [-65 (A-->G), -55 (T-->C), -36 (C-->A)], were also revealed. These changes are either linked in cis with other mutations or are responsible for thalassemias or for positive regulatory effect in delta-globin gene expression. The proposed experimental strategy consists of an accurate, rapid, safe and inexpensive screening procedure for establishing the molecular basis of delta-globin gene defects, suitable for the application for both research and diagnostics.

Electrophoresis, Polyacrylamide Gel↗

Hb Lepore (Pylos)/Hb S compounds heterozygosity in two Greek families.

We have studied three compound heterozygotes for Hb Lepore ("Pylos")/HbS hemoglobin, a combination quite uncommon in the literature. It is of interest that while two of these cases are clinically similar to those thus far reported, the third one is free of symptoms and the diagnosis was put incidentally. This mild condition may be due to the high level of fetal hemoglobin produced.

Adult↗

Pulmonary perfusion during lung transplant rejection and experimental pneumonia.

Six left lung allotransplants were performed in healthy mongrel dogs. Immunosuppression was established with cyclosporine (15 mg/kg/day p.o.) from the day of transplantation for 30 days. Another group of animals (n = 3) was used to produce acute experimental pneumonia by instilling 4-6 ml of a 10(8) CFU suspension of Pseudomonas aeruginosa into the right lower lobe. Dynamic perfusory lung scintigraphy (DPLS) was performed before transplant/pneumonia (control), during acute rejection/pneumonia as detected radiologically, and after treatment with methylprednisolone (1 g/day for 3 days i.v.) (transplant group) or antibiotics (pneumonia group). Seroalbumin macroaggregates (5-8 McI) marked with 99-mTc were injected into the cephalic vein and the percentage of perfusion to each lung was determined. Eight acute rejection episodes were detected. DPLS showed similar perfusion to each lung, whereas during acute rejection perfusion was significantly reduced by almost 30%. Perfusion was reestablished to control levels after treatment with methylprednisolone. Reduction in perfusion correlated with radiological rejection grading. No reduction in left lung perfusion was detected in pneumonia animals. In conclusion, acute rejection reduces perfusion to the transplanted lung as measured by DPLS. Treatment restores normal perfusion.

Animals↗

Effects of fasting and diabetes on some enzymes and transport of glutamate in cortex slices or synaptosomes from rat brain.

Phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase (GAD) were assayed in homogenates and synaptosomes obtained from starved (48 hr or 120 hr) and diabetic (streptozotocin) rat brain cortex. Glutamine synthetase (GS) was assayed in homogenates, microsomal and soluble fractions, from brain cortex of similarly treated rats. L-Glutamate uptake and exit rates were determined in cortex slices and synaptosomes under the same conditions. The specific activity (s.a.) of PAG, a glutamate producing enzyme, decreased (50%) in the homogenate after 120-hr starvation. In synaptosomes it decreased (25%) only after 48-hr starvation. The s.a. of GAD and GS, which are glutamate-consuming enzymes, were progressively increased with time of starvation, reaching 39% and 55% respectively after 120 hr. GS in the microsomes or the soluble fraction and GAD in the synaptosomes showed no change in s.a. under these conditions. Diabetes increased (40%) microsomal GS s.a. and decreased GAD s.a. (18%) in the homogenate. The L-glutamate uptake rate was decreased (48%) by diabetes in slices but no in synaptosomes. It is suggested that a) enzymes of the glutamate system respond differently in different subcellular fractions towards diabetes or deprivation of food and b) diabetes may affect the uptake system in glial cells but not in neurons.

Animals↗