PubMed Health⌕ Search

Biomedical subjects

T Vassilakopoulos

Publications and source records attributed to T Vassilakopoulos.

At least 19 recordsLinked to original sources
PubMed2001

Association of allelic loss at the FHIT locus and p53 alterations with tumour kinetics and chromosomal instability in non-small cell lung carcinomas (NSCLCs).

The FHIT gene, located at the FRA3B fragile site of chromosome 3p14.2, encodes a 16.8 kD homologue of the yeast enzyme diadenosine tetraphosphate (Ap(4)A) hydrolase. Frequent allelic losses at this region in various malignancies, including non-small cell lung carcinomas (NSCLCs), imply that FHIT may represent a tumour suppressor gene (TSG). Increasing evidence suggests that multiple TSG impairment has a synergistic effect on tumour growth. The present study of 67 NSCLCs investigated the allelic imbalance (AIm) within the FHIT locus and its relationship with p53 abnormalities, kinetic parameters [proliferative activity or proliferation index (PI) and apoptotic index (AI)], and ploidy status of the carcinomas. Allelic imbalance at FHIT was observed in 35 out of 55 informative (heterozygous: H) cases (64%). Similar frequencies of loss of heterozygosity (LOH) were noticed among squamous cell lung carcinomas and adenocarcinomas. The high percentage of AIm in stage I tumours (71%) is indicative of its relatively early involvement in NSCL carcinogenesis. No association was found between LOH at FHIT, kinetic parameters, and ploidy status of the tumours. Concurrent loss at FHIT and p53 overexpression [FHIT(LOH)/p53(P)] was the most frequent pattern and was observed in 39% of the informative cases. The latter pattern was not associated with smoking, supporting the hypothesis that in patients with a history of tobacco exposure, FHIT allelic loss may not be a consequence of p53 checkpoint defects, but the outcome of tobacco-induced mutagenesis. Statistically significant differences in the presence of FHIT(LOH)/p53(P) and FHIT(LOH)/p53(N) patterns were noted at the proliferative and apoptotic level, whereas ploidy was similar amongst all groups, implying that wild-type (wt) p53 may play a safeguard role against altered FHIT function. However, the possibility of a masking effect from wt p53 cannot be excluded, since the FHIT(LOH)/p53(P) profile demonstrated a higher growth index (GI=PI/AI mean value ratio) than FHIT(H)/p53(P) (32 vs. 8), although this was not significant. Further studies are needed in order to elucidate the role of FHIT and its relationships with other cell-cycle regulatory molecules involved in NSCL carcinogenesis.

Acid Anhydride Hydrolases↗
PubMed2001

Diagnostic and prognostic significance of squamous cell carcinoma antigen in non-small cell lung cancer.

Squamous cell carcinoma antigen (SCC-Ag) is a glycoprotein secreted by non-small cell lung tumours (NSCLC). This study investigated the diagnostic and prognostic significance of SCC-Ag in NSCLC. Receiver operating characteristic (ROC) curve analysis was used to test the diagnostic performance of the SCC-Ag and determine the optimal threshold value in a group of 100 NSCLC patients undergoing surgery and 50 age matched healthy controls. This threshold was then prospectively validated in a group of 53 patients and 49 healthy controls. The prognostic significance of the preoperative SCC-Ag level and its postoperative decrease were tested using univariate and multivariate proportional hazard models. The area under the ROC curve was 0.71+/-0.04, and the best cutoff value was 1.4 ng/ml. This discriminated patients in the validation group, with a sensitivity of 0.55 and a specificity of 1.0. The hazard ratio was 0.144 (95% CI 0.074-0.281) for the postoperative decrease in the SCC Ag, and 5.823 (3.299-10.278) for the preoperative SCC Ag level. Multivariate analysis revealed that only disease stage and patients' age are strong prognostic factors for survival. In conclusion, the SCC-Ag serum level has moderate diagnostic role in NSCLC. Both the preoperative SCC-Ag level and its postoperative decrease have prognostic significance, yet inferior to the disease stage and the patient's age.

Adenocarcinoma↗
PubMed2001

Evaluation of DNA topoisomerase IIalpha expression provides independent prognostic information in non-Hodgkin's lymphomas.

AIMS: In view of the dual role that DNA topoisomerase IIa (TopoIIa) plays as a cell proliferation marker and as a possible indicator of chemosensitivity, we investigated its expression in non-Hodgkin's lymphomas (NHL) in relation to conventional clinicopathological parameters, cell proliferation (as defined by Ki67 immunoreactivity), response to therapy and patient outcome. METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissues from 153 patients with NHL were immunohistochemically stained for TopoIIalpha. Patients were followed up until death (n = 63) or for an average of 68 months (median 64 months, n = 90). The percentage of TopoIIalpha positive cells (TopoIIalpha LI) increased with grade (P < 0.001), extranodal location (P = 0.05) and Ki67 LI (P = 0.01, r = 0.673). In most cases (58%), Ki67 LI exceeded TopoIIalpha LI (TopoIIalpha/Ki67 < 1), especially within the indolent group (P < 0.001). TopoIIalphaLI, Ki67LI and TopoIIalpha/Ki67 ratio were all adversely related to overall survival in univariate analysis, though their significance was not maintained after adjustment for grade. In multivariate analysis high TopoIIalpha/Ki67 ratio and high TopoIIalpha LI independently predicted shortened overall and post-relapse survival, respectively. Most importantly, low TopoIIalpha/Ki67 ratio was the only independent predictor of diminished disease-free survival. However, there was no relationship between TopoIIalpha expression and response. CONCLUSIONS: Our results suggest that evaluation of TopoIIalpha expression and TopoIIalpha/Ki67 ratio as cell proliferation markers provides independent prognostic information in relation to post-relapse and overall survival. Furthermore, TopoIIalpha/Ki67 ratio appears to play a key role in the identification of patients prone to early relapse.

Adolescent↗
PubMed2001

Pulmonary hypertension, interstitial lung fibrosis, and lung iron deposition in thalassaemia major.

Although restrictive lung disease is the predominant abnormality of pulmonary function in patients with thalassaemia major (TM), its aetiology and its association with pulmonary hypertension (PH) detected in some patients with TM remains unknown. We report a patient with TM, iron overload, frequent pulmonary infections, and progressive severe precapillary PH over the previous 5 years. A severe restrictive pattern and interstitial lung fibrosis were revealed by pulmonary function tests and high resolution computed tomography, respectively. This presentation suggests that interstitial fibrosis may complicate lung involvement in TM and can significantly contribute to the development of PH.

Adult↗
PubMed2001

Echocardiographic and ambulatory electrocardiographic findings in elite water-polo athletes.

The aim of this study was to investigate the echocardiographic and electrocardiographic findings in top water-polo athletes and test the hypothesis that their hearts exhibit dilatation associated with hypertrophy secondary to the mixed type (isotonic and isometric) of exercise they are subjected to. Eighteen athletes of the Greek national water-polo team and 15 healthy sedentary men serving as controls were studied. All underwent an echocardiogram, a standard 12-lead ECG and 24-h ECG monitoring. In athletes, as compared to healthy controls, an increase was detected in the following indices: left ventricular (LV) end-diastolic diameter index (EDDI-LV) (by 10%; P = 0.02), interventricular septal thickness (IVS) (by 32%; P<0.001), thickness of the posterior wall (PW) (by 29%; P<0.001), relative wall thickness (IVS + PW/EDD-LV) (by 12%; P < 0.001) and LV mass index (by 82%; P < 0.001). Mild asymmetric thickening of the septum (IVS/PW = 1.40 and 1.37) was measured in two athletes. LV fractional shortening was normal. Standard 12-lead ECG abnormalities (LV hypertrophy or abnormal repolarization pattern) were observed in 33% of athletes. Athletes had sinus bradycardia during day and night, respiratory arrhythmia (RA) (83% vs 40% of controls; P = 0.03) and sinus pauses (SP) (39% vs 0% of controls; P = 0.02), with occassional arrhythmias and conduction abnormalities. We conclude that top water-polo athletes have dilatation combined with substantial hypertrophy and normal systolic function of the LV In addition they present bradycardia, RA and SP, with occassional arrhythmias and conduction abnormalities.

Adaptation, Physiological↗
PubMed2000

Influence of oxygen supply on activation of group IV muscle afferents after low-frequency muscle stimulation.

Anaerobic muscle metabolism and local release of inflammatory mediators play key roles in the mechanism of postfatigue-induced activation of group IV muscle afferents. The present study focused on activation of these muscle afferents after a 3-min period of low-frequency muscle stimulation (LFMS) in different conditions of muscle oxygenation, such as occur in patients with respiratory insufficiency and subjects living at high altitude. In anesthetized rabbits, spontaneous activity of group IV afferents (conduction velocity = 1.52 +/- 0.13 m.s(-1)) from the tibialis anterior muscle was recorded at rest (baseline) and then after LFMS under normoxic (PaO(2) = 113 mmHg), hyperoxic (PaO(2) = 186 mmHg), or hypoxic (PaO(2) = 35 mmHg) conditions. The maximal force decay at the end of LFMS did not differ significantly with respect to conditions of muscle oxygenation. Compared with normoxia, hypoxia significantly increased the baseline activity of group IV muscle afferents, whereas no effect was noted when hypoxia followed a period of hyperoxia. LFMS-induced activation of group IV afferents occurred in all circumstances, except when hypoxia was first tested. The activation of group IV muscle afferents after LFMS was markedly reduced when hypoxia followed normoxia (+14% versus +27%) or hyperoxia (+55% versus +144%), whereas it was accentuated when hyperoxia followed hypoxia (+25% versus +8%). We concluded that the sensorimotor control of skeletal muscles may be altered during acute hypoxia but facilitated after reoxygenation.

Animals↗
PubMed2000

A role for transoesophageal echocardiography in the early diagnosis of catastrophic antiphospholipid syndrome.

We describe a previously healthy 28-year-old woman who presented with the clinical picture of large vessel occlusions (stroke with left hemiparesis, myocardial infarction) and developed multi-organ failure (i.e. kidneys, heart, brain, liver, blood, skin) over a very short period of time. Peripheral blood smear was consistent with thrombotic thrombocytopenic purpura. Transesophageal echocardiogram was supportive of the diagnosis of catastrophic antiphospholipid syndrome (CAPS), revealing Libman-Sacks endocarditis. Blood cultures were negative, anticardiolipin antibodies were highly increased and lupus anticoagulant was positive. Cerebral and coronary angiograms were negative, suggesting possible microthrombotic occlusive disease in the setting of CAPS.

Acute Disease↗
PubMed2000

The analgesic efficacy of intravenous tenoxicam as an adjunct to patient-controlled analgesia in total abdominal hysterectomy.

UNLABELLED: Nonsteroidal antiinflammatory drugs may reduce postoperative opioid consumption. We evaluated the analgesic efficacy of preoperatively administered tenoxicam in patients undergoing total abdominal hysterectomy. Patients were randomly assigned to receive IV either normal saline 4 mL (Group NS), tenoxicam 20 mg (Group T20), or tenoxicam 40 mg (Group T40) before the induction of anesthesia in a double-blinded fashion. Patient-controlled analgesia with fentanyl was used to assess postoperative opioid requirements. Pain was evaluated by visual analog scale at 2, 4, 6, 8, and 24 h postoperatively. Intraoperative bleeding as assessed by the surgeon, incidence of nausea, and gastrointestinal symptoms were recorded. No statistically significant difference was identified between groups in fentanyl consumption or pain scores. The incidence of nausea was similar in all groups. Two patients in Group T20 and two in Group T40 exhibited mild gastrointestinal symptoms. Intraoperative oozing was noted in two patients in Group T40. We conclude that patients undergoing total abdominal hysterectomy and receiving fentanyl via patient-controlled analgesia postoperatively do not benefit from tenoxicam pretreatment. On the contrary, the drug may be associated with an increased incidence of side effects. IMPLICATIONS: The preoperative administration of 20 or 40 mg IV tenoxicam does not reduce fentanyl consumption via Patient-Controlled Analgesia, compared with placebo, after total abdominal hysterectomy. Additionally, tenoxicam may increase intraoperative bleeding and gastrointestinal side effects.

Adult↗
PubMed2000

Contribution of pain to inspiratory muscle dysfunction after upper abdominal surgery: A randomized controlled trial.

Upper abdominal surgery causes respiratory muscle dysfunction. Multiple factors have been implicated in the occurrence of such dysfunction; however, the role of pain remains unclear. To elucidate the role of pain, we studied 50 patients undergoing elective upper abdominal surgery in a randomized, controlled investigation. Inspiratory and expiratory muscle function were assessed through sniff mouth pressure (Psniff) and maximal expiratory pressure (MEP), respectively. Pain during the pressure maneuvers was assessed with a visual analog scale (VAS). Measurements were made before surgery (Session 1), 24 h after surgery (Session 2), and 1 h later, after intramuscular administration of pethidine (analgesia group) or placebo (placebo group) (Session 3). To evaluate the effect of pain, we used a mixed-effects model with random intercept, having either Psniff or MEP as the dependent variable and both surgical operation and the level of pain as fixed effects. Upper abdominal surgery decreased Psniff in both the analgesia and placebo groups (from 70 +/- 15 to 42 +/- 11 cm H(2)O [p < 0.05] in the analgesia group, and from 69 +/- 15 to 42 +/- 10 cm H(2)O [p < 0.05] in the placebo group). Intramuscular pethidine caused an increase in Psniff to 56 +/- 14 cm H(2)O (p < 0.05), whereas placebo had no effect. Pain increased comparably after upper abdominal surgery in both groups (from 0.3 +/- 0.6 to 4.4 +/- 1.5) [p < 0.05] in the analgesia group and from 0.4 +/- 0.5 to 4.3 +/- 1.5 [p < 0.05] in the placebo group). Intramuscular pethidine decreased pain as measured by VAS score to 2.1 +/- 1.0 (p < 0.05) in the analgesia group, whereas placebo had no effect. Psniff had a statistically significant relationship to pain (p < 0.001). Adjusting for the occurrence of surgical operation did not affect this result. MEP showed the same tendency as Psniff, but the observed changes did not reach statistical significance. We conclude that pain contributes to inspiratory muscle dysfunction after upper abdominal surgery.

Abdomen↗
PubMed2000

Expiratory flow limitation and intrinsic positive end-expiratory pressure at zero positive end-expiratory pressure in patients with adult respiratory distress syndrome.

It has been suggested that in patients with adult respiratory distress syndrome (ARDS), intrinsic positive end-expiratory pressure (PEEPi) is generated by a disproportionate increase in expiratory flow resistance. Using the negative expiratory pressure (NEP) technique, we assessed whether expiratory flow limitation (EFL) and PEEPi were present at zero PEEP in 10 semirecumbent, mechanically ventilated ARDS patients. Because bronchodilators may decrease airway resistance, we also investigated the effect of nebulized salbutamol on EFL, PEEPi, and respiratory mechanics in these patients, and in seven patients we measured the latter variables in the supine position as well. In the semirecumbent position, eight of the 10 ARDS patients exhibited tidal EFL, ranging from 5 to 37% of the control tidal volume (VT), whereas PEEPi was present in all 10 subjects, ranging from 0.4 cm H(2)O to 7.7 cm H(2)O. The onset of EFL was heralded by a distinct inflection point on the expiratory flow-volume curve, which probably reflected small-airway closure. Administration of salbutamol had no statistically significant effect on PEEPi, EFL (as %VT), or respiratory mechanics. EFL (%VT) and PEEPi were significantly higher in the supine position than in the semirecumbent position, whereas the other respiratory variables did not change. Our results suggest that in the absence of externally applied PEEP, most ARDS patients exhibit EFL associated with small-airway closure and a concomitant PEEPi.

Adult↗
PubMed2000

Contribution of expiratory muscle pressure to dynamic intrinsic positive end-expiratory pressure: validation using the Campbell diagram.

In spontaneously breathing (SB) patients expiratory muscle contraction leads to an overestimation of dynamic intrinsic PEEP (PEEP(i),dyn). To quantify this overestimation, PEEP(i),dyn measured with the esophageal balloon technique was corrected for the increase in Pga over the course of expiration (Pga,exp rise), for the whole decay of Pga during inspiration (Pga,total decay) or for the part of Pga decay restricted between the onset of inspiratory effort and the point of zero flow (Pga,zf decay). Corrections were compared with the reference PEEP(i),dyn (PEEP(i),dyn ref ), calculated by using the Campbell diagram. In 15 ventilator-dependent, SB, and actively expiring patients, we found that the difference PEEP(i),dyn - Pga, total decay (mean +/- SD, 5.7 +/- 1.9 cm H(2)O) was quite similar to PEEP(i),dyn ref (5.3 +/- 1.9 cm H(2)O). Their mean difference was 0. 37 cm H(2)O with limits of agreement -0.09 to 0.83 cm H(2)O, indicating strong agreement between these methods. PEEP(i),dyn - Pga, exp rise (6.0 +/- 2.1 cm H(2)O) was also similar to PEEP(i),dyn ref. Their mean difference was 0.72 cm H(2)O with limits of agreement -1. 69 to 3.13 cm H(2)O, indicating good agreement. In contrast, mean difference of PEEP(i),dyn - Pga,zf decay and PEEP(i),dyn ref was 3. 14 cm H(2)O with limits of agreement -0.46 to 6.74 cm H(2)O, indicating lack of agreement. The error in measurement due to the subtraction of Pga,zf decay from PEEP(i),dyn (i.e., [PEEP(i),dyn - Pga,zf decay] - PEEP(i),dyn ref ) was proportional to the intensity of expiratory muscle contraction, as expressed by the Pga,exp rise (r = 0.903, p < 0.001). We conclude that in actively expiring patients an adequate correction of PEEP(i),dyn for the overestimation caused by expiratory muscle contraction can be made by subtracting either Pga,total decay or Pga,exp rise from PEEP(i), dyn, the former achieving the best performance.

Abdomen↗
PubMed1999

Weaning from mechanical ventilation.

For most mechanically ventilated patients, weaning can be accomplished quickly and easily. However, there is a smaller group of ventilated patients who fail to wean and remain ventilator-dependent. These patients account for a significant amount of health care costs and pose a great challenge for clinicians. Detailed knowledge of the etiology and pathophysiology of weaning failure is very important for the "treatment" of difficult to wean patients, and is thoroughly presented in this article. Based on this physiological background, strategies and techniques are proposed that are useful for the gradual transition to spontaneous ventilation.

Humans↗
PubMed1999

Strenuous resistive breathing induces proinflammatory cytokines and stimulates the HPA axis in humans.

Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), powerful stimulants of the hypothalamic-pituitary-adrenal (HPA) axis, increase in response to whole body exercise. Strenuous inspiratory resistive breathing (IRB), a form of clinically relevant "exercise" for the respiratory muscles, produces beta-endorphin through a largely unknown mechanism. We investigated (in 11 healthy humans) whether strenuous IRB produces proinflammatory cytokines and beta-endorphin in parallel with stimulation of the HPA axis, assessed by concurrent measurement of ACTH. Subjects underwent either severe [at 75% of maximal inspiratory pressure (P(m) (max))] or moderate (at 35% of P(m) (max)) IRB. Plasma cytokines, beta-endorphin, and ACTH were measured at rest (point R), at the point at which the resistive load could not be sustained (point F), and at exhaustion [15 min later (point E)]. During severe IRB, IL-1beta increased from 0.83 +/- 0.12 pg/ml at point R to 1.88 +/- 0. 53 and 4.06 +/- 1.27 pg/ml at points F and E, respectively (P < 0. 01). IL-6 increased from 5.30 +/- 1.02 to 10.33 +/- 2.14 and 11.66 +/- 2.29 pg/ml at points F and E, respectively (P = 0.02). ACTH and beta-endorphin fluctuated from 20.87 +/- 5.49 and 25.03 +/- 3.97 pg/ml at point R to 22.97 +/- 4.41 and 26.32 +/- 3.93 pg/ml, respectively, at point F and increased to 46.96 +/- 8.55 and 40.32 +/- 5.94 pg/ml, respectively, at point E (P < 0.01, point E vs. point F). There was a positive correlation between the IL-6 at point F and the ACTH and beta-endorphin at point E (r = 0.88 and 0.94, respectively; P < 0.01) as well as between the increase in IL-6 (between points R and F) and the increases in ACTH and beta-endorphin (between points F and E, r = 0.91 and 0.92, respectively; P < 0.01). Moderate IRB did not produce any change. We conclude that severe IRB produces proinflammatory cytokines and stimulates the HPA axis in humans secondary to the production of cytokines (especially IL-6).

Adrenocorticotropic Hormone↗