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G Eliopoulos

Publications and source records attributed to G Eliopoulos.

At least 19 recordsLinked to original sources
PubMed2002

Molecular characterization of vancomycin-resistant Enterococci repopulating the gastrointestinal tract following treatment with a novel glycolipodepsipeptide, ramoplanin.

We characterized baseline and repopulating stool isolates recovered during a phase II trial of ramoplanin for the treatment of patients with stool carriage of vancomycin-resistant enterococci (VRE). Repopulation with a strain with a related genotype was found in 74, 60, and 53% of individuals in groups treated with placebo, 100 mg of ramoplanin, and 400 mg of ramoplanin, respectively. All ramoplanin-treated patients with a culture positive for VRE at day 7 had a relapse caused by a genotypically related isolate. In ramoplanin-treated patients, antibiotics with activities against anaerobic organisms were associated with positive cultures on day 7 (relative risk [RR] = 8.8; P = 0.004), and the avoidance of such antibiotics was significantly associated with culture negativity through day 21 (RR = 0.16; P = 0.02).

Anti-Bacterial Agents↗
PubMed2001

Acute and chronic neutropenias. What is new?

Recently, some of the mechanisms and consequences in the severe chronic neutropenias (e.g. the neutrophil elastase gene mutations and the risk to progress to myelodysplasia and acute leukaemia) and in drug-induced agranulocytosis (e.g. the apoptosis-inducing ability of metabolites of clozapine) have been elucidated, and new aspects of autoimmune and the large granular lymphocyte syndrome were described (e.g. aberrant elaboration of Fas-ligand causing neutrophil apoptosis). Investigations of the mild to moderate chronic neutropenias have shown the significance of interactions between the myeloid development and the immune network (e.g. relations to immunoglobulin aberrations). Granulocyte-colony stimulation factor (G-CSF) is widely used in patients with severe chronic neutropenia, however, its use in other conditions is mostly based on anecdotal evidence. In addition, immune modulating regimens, such as metothrexate, ciclosporine and monoclonal antibodies, are increasingly employed for the autoimmune neutropenias.

Acute Disease↗
PubMed2001

Splenic involvement in lymphomas. Evaluation on serial CT examinations.

PURPOSE: To prospectively evaluate changes in splenic volume (SV) on serial CT of patients with lymphoma and correlate them with other indicators of the disease process. MATERIAL AND METHODS: SV was calculated in 290 abdominal CT examinations of 58 consecutive adults with lymphoma (42 non-Hodgkin's lymphoma, 16 Hodgkin's disease). Each patient had one CT investigation before, 2 during chemotherapy and 2 post-chemotherapy. The changes in SV were correlated with clinical, laboratory and other imaging indicators of the disease process. RESULTS: Three groups of patients were identified. Group A (n=20) presented no changes in SV, showed no splenic parenchymal abnormalities and had normal SV and serum lactic dehydrogenase (S-LDH). Group B (n=25) presented a decrease in SV during treatment suggesting response to therapy. Splenic parenchymal abnormalities (n=5) and other subdiaphragmatic sites of involvement (n=20) underwent remission during treatment. Eighteen patients with high S-LDH at presentation showed normal values during therapy. Group C (n=12) showed an increase in SV post-therapy associated with manifestations of disease recurrence. The S-LDH levels were elevated in 10 patients at the same time. CONCLUSION: Quantitatively assessed splenic size on CT may serve as an indicator of splenic involvement in the course of lymphomas.

Adolescent↗
PubMed2000

Clinical implications of stenotrophomonas maltophilia resistant to trimethoprim-sulfamethoxazole: a study of 69 patients at 2 university hospitals.

We conducted a retrospective case study at 2 tertiary care centers to determine the clinical implications of trimethoprim-sulfamethoxazole resistant Stenotrophomonas maltophilia (TSRSM). Of 69 reviewed cases (mean age, 57 y; male gender, 70%), 40 (58%) were classified as infections associated with TSRSM (respiratory tract, 14; soft tissue, 11; bloodstream, 8; other sites, 7). Severe underlying comorbidities (86%) and previous antibiotic exposure (99%) were common. Cefotetan (susceptibility, 55%), chloramphenicol (49%) and ticarcillin-clavulanate (45%) showed the highest in vitro activity against TSRSM, but were seldom used for therapy (7%). Among the 40 infected cases, 8 developed sepsis disorders and 8 died. Only 1 death could be directly attributed to autopsy-proven TSRSM infection (pneumonia). McCabe score (p = 0.03) and organ dysfunction (p = 0.006) were associated with an increased risk of death in infected patients; exposure to appropriate therapy tended to be protective against death (p = 0.08). 22 infected patients were treated medically; an additional procedure was necessary to clear the infection in 18 cases (surgery, 13; catheter removal, 5). Isolation precautions were rarely exercised, even in the presence of panresistant isolates. In summary, TSRSM-related infections occurred in severely ill patients with extensive exposure to the health-care system, and often required invasive procedures for cure. Infections were directly associated with severe morbidity, and tended to have an indirect rather than a direct impact on mortality.

Anti-Bacterial Agents↗
PubMed2000

Expression of p53, p21/waf1, bcl-2, bax, Rb and Ki67 proteins in Hodgkin's lymphomas.

The aim was to investigate the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in Hodgkin's lymphomas (HL) and correlate expression patterns with the histotype and the Epstein-Barr Virus (EBV) status. Paraffin-sections from 56 cases of HL (18 nodular sclerosis and 38 mixed cellularity) and from ten "reactive" lymph nodes were investigated. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in Hodgkin and Reed-Sternberg (HRS) cells in 35/56, 56/56, 24/56, 23/56, 56/56 and 56/56 cases of HL, respectively. No correlation was found between the expression of each protein and the EBV status or the histotype of HL. Comparison between p53 and p21 staining revealed two patterns: a) p53+/p21+ (35 cases); and b) p53-/p21+ (21 cases). The pattern p53+/p21+ suggests wild type p53 protein able to induce the expression of p21 while the p53-/p21+ pattern suggests p53-independent p21 expression. These results are consistent with the interpretation that inactivating p53 gene mutations may be rare in HL. Comparison between bcl-2 and bax staining showed a statistically significant relationship (p<0.001) for coexpression (19 cases) or absence of expression of both proteins (28 cases) in HRS cells. In contrast, bax expression was observed in most lymphoid cells in all "reactive" lymph nodes. Since the proapoptotic bax protein may act as tumour suppressor it is possible that the absence of this protein in HRS cells in a substantial proportion of HL may confer growth advantage and play a role in their pathogenesis. This could suggest bax gene alterations in some HL since in other studies acute lymphoblastic leukaemia cell lines demonstrate bax gene mutations with loss of bax immunoexpression. Another possibility is that reduced bax expression may be due to post transcriptional regulation, as was described in lymphoma cell lines. Comparison between Rb and Ki67 staining disclosed two main deviations from the normal parallel relationship in reactive lymph nodes: a) 2 cases with low Rb and high Ki67 expression possibly reflecting loss of Rb expression due to chromosome loss or to other abnormalities in the structure or the expression of Rb gene; and b) 9 cases with high RB and low Ki67 possible reflecting an attempt of Rb protein in excess to induce cell cycle arrest. Taken together, our findings provide combined immunohistological evidence for deregulated expression of cell-cycle and apoptosis-related proteins, that may play a role in the pathogenesis of HL.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMed1999

Immunohistochemical detection of p53, mdm2, waf1/p21, and Ki67 proteins in bone marrow biopsies in myelodysplastic syndroms, acute myelogenous leukaemias and chronic myeloproliferative disorders.

The aim oof this study was to investigate the immunohistochemical expression of p53, mdm2, and waf1/p21 proteins in myelodysplastic syndromes (MDS), acute myelogenous leukaemias (AML), and chronic myeloproliferative disorders (CMPD). Paraffin-sections of bone marrow biopsies from 30 cases of MDS (6 cases of RAEB and RAEB-T) 22 AML (4 cases occurring in the setting of MDS), 16 chronic myeloproliferative disorders (CMPD), and 10 cases without alterations were investigated by immunohistochemistry for p53, waf1/p21, mdm2 and Ki67 proteins. P53 was detected in immature myeloid cells in 6/30 MDS (20%) and in 6/22 AML (27%) while it was not expressed in CMPD. Of the 6 p53 positive AML, 3 occurred as evolution of MDS and 3 were de novo acute leukaemias. Waf1/p21 was detected in 5/22 (23%) AML in immature myeloid cells. Waf1/p21 was also expressed in 18/30 (60%) MDS and 10/16 (63%) CMPD in variable proportion (5-25%) of the mature myeloid cells and megakaryocytes. Waf1/p21 was not detected in immature myeloid cells in MDS and CMPD. Mdm2 protein was expressed in 3/30 (10%) MDS in the immature myeloid cells and in 1/22 AML in blastic cells. The combined immunophenotypes of immature myeloid cells of MDS were: p53+/mdm2+/waf1-: 3, p53+/mdm2-/waf1-: 3, while the immunohistochemical patterns of AML were: p53+/mdm2-/waf1-: 4, p53+/mdm2+/waf1+: 1, p53+/mdm2-/waf1+: 1, p53-/mdm2-/waf1+: 3. Ki67/MIB1 staining was found in at least 30% of immature myeloid cells in MDS and AML and in at least 20% of these cells in CMPD. In conclusion, our results indicate that p53 protein is overexpressed in the myeloid lineage in a proportion of AML and MDS, while is not detected in CMPD and normal bone marrow, p53 expression was much more frequent in AML occurring as an evolution of MDS than in de novo AML. The combined immunophenotypes of p53 positive AML and MDS suggest that p53 overexpression may be due to mutation, in some AML and MDS cases with the p53+/mdm2-/waf1- phenotype. However, it would be also possible that p53 protein accumulation is not related to p53 mutation but to inhibition of p53/mdm2 binding due to mdm2 defects and/or other events related to cell stress signals. On the other hand, waf1/p21 protein overexpression without p53 expression in some AML could be p53-independent and may represent an attempt to control the high proliferation rate which was evidenced by Ki67/MIB1 immunostaining. However, the possibility of p21 to arrest cell-cycle, in these cases of AML, seems to be overridden, suggesting that cell-cycle deregulation may be involved in a proportion of AML.

Biopsy↗
PubMed1998

Specific depletion of alloreactive T cells in HLA-identical siblings: a method for separating graft-versus-host and graft-versus-leukaemia reactions.

Accumulating evidence indicates that alloreactive donor T cells confer both graft-versus-host (GVH) and graft-versus-leukaemia (GVL) reactivity following allogeneic bone marrow transplantation. We have developed a method to deplete alloreactive donor T cells with an immunotoxin targeting the alpha chain of the IL-2 receptor. In patients with chronic myeloid leukaemia and their HLA-identical sibling donors, we measured donor helper T-lymphocyte precursor frequencies (HTLPf) against recipient peripheral blood mononuclear cells (PBMNC; donor versus host), recipient leukaemia cells (donor versus leukaemia) and third-party PBMNC, before and after the depletion. In seven pairs there was a 4.3-fold reduction of donor-versus-host HTLPf (P=0.017), without a significant change in the donor frequencies against third party (P=0.96). In eight further donor-recipient pairs, immunotoxin-depleted donor versus patient PBMNC HTLPf 4.5-fold (mean 1/155,000 before and 1/839,000 after depletion, P=0.007). There was a smaller non-significant 1.8-fold reduction in donor-versus-leukaemia HTLPf from 1/192,000 to 1/334,000 (P=0.19). These results suggest that selective T-cell depletion can significantly deplete donor anti-host reactivity while conserving anti-leukaemia reactivity in HLA-matched donor-recipient pairs.

Bone Marrow Transplantation↗
PubMed1996

p53 protein expression in non-Hodgkin's lymphoma. Comparative study with the wild type p53 induced proteins mdm2 and p21/waf1.

Aims-To investigate the pattern of expression of p53 protein and two wild type p53 induced proteins (mdm2 and p21/waf1) as an indirect way of assessing p53 gene status in non-Hodgkin's lymphoma.Methods-Formalin fixed, paraffin wax embedded tissue from 87 cases of nodal non-Hodgkin's lymphoma, comprising 52 high grade and 35 low grade tumours, was stained by immunohistochemistry for p53, mdm2 and p21/waf1 proteins.Results-p53, mdm2 and waf1/p21 proteins were expressed in 36/52, 21/52 and 31/52 high grade and 3/35, 21/35 and 3/35 low grade non-Hodgkin's lymphomas, respectively. Parallel p53/mdm2 protein expression was found in 23 cases (21 high grade and two low grade). These 23 cases were also positive for p21/waf1 protein expression. Discordant p53 positive/mdm2 negative protein expression was found in 16 cases (15 high grade and one low grade). Eleven (10 high grade and one low grade) of these 16 cases were p21/waf1 positive and the remaining five high grade non-Hodgkin's lymphomas were p21/waf1 negative. Mdm2 and p21/waf1 proteins were not expressed in the absence of p53 protein expression.Conclusions-p53, mdm2 and waf1/p21 protein expression is more frequently associated with aggressive histotypes of non-Hodgkin's lymphoma. Parallel expression of p53, mdm2 and p21 proteins may represent non-Hodgkin's lymphomas with a wild type p53 gene as mdm2 and p21 proteins can be induced by the wild type gene. In these cases p53 protein expression may result from stabilisation via complex formation with the mdm2 protein. This could be important in the pathogenesis of these cases as mdm2 may deregulate the p53 dependent growth suppressive pathway. Discordant p53 positive/mdm2 negative/p21 negative protein expression may represent non-Hodgkin's lymphoma with p53 gene mutations unable to activate expression of mdm2 and p21 proteins. Non-Hodgkin's lymphoma with p53 positive/mdm2 negative/p21 positive protein expression may have either wild type p53 with deregulated mdm2 gene expression or mutated p53 gene with p53 independent p21 expression.

Journal Article↗
PubMed1994

Comparison of tests for detection of methicillin-resistant Staphylococcus aureus in a clinical microbiology laboratory.

By microdilution testing, 186 of 1,450 clinical isolates of Staphylococcus aureus were preliminarily classified as oxacillin resistant (MIC > or = 4 micrograms/ml); 15 of these isolates gave conflicting results by alternative methods and were studied further. Only 2 of these (MIC > 4 micrograms/ml) were mecA positive; 13 were inhibited by oxacillin at 4 micrograms/ml. Significant numbers of S. aureus strains classified as resistant with an oxacillin MIC of 4 micrograms/ml may prove susceptible by other methods.

Base Sequence↗
PubMed1994

'Fetal' erythropoiesis following bone marrow transplantation as estimated by the number of F cells in the peripheral blood.

The aim of this study was to define factor(s) influencing fetal erythropoiesis following bone marrow transplantation. Thirty-one transplanted patients (14 males, 17 females) were studied. The underlying diseases were chronic myelogenous leukaemia (CML, 18 patients), acute myeloblastic leukaemia (AML, 7 patients) and acute lymphoblastic leukaemia (ALL, 6 patients). Reticulocyte and peripheral F cell estimation was carried out in donors and patients before transplantation and repeatedly during recovery. For F cell estimation, an indirect immunofluorescence assay was utilized. A significant increase above pre-BMT values in the percentage of F cells was observed in all patients from days 11 to 40 after transplantation. The increase of F cells on days 15, 18, 25, 32, 40 and 50 after transplantation was statistically significant in 14 patients who had shown an increase of F cells following chemotherapy (high responders) compared with the remaining 17 patients who did not respond so significantly. This finding supports the influence of the host bone marrow micro environment. The nature of the mechanisms operating remains to determined.

Adolescent↗
PubMed1992

Vancomycin-resistant Enterococcus faecium in hospitalized children.

OBJECTIVE: Determine the epidemiology and risk factors for colonization with vancomycin-resistant Enterococcus faecium. DESIGN: Survey; case-control study. SETTING: Children's hospital. PATIENTS: Pediatric oncology patients. INTERVENTION: Contact isolation, restriction of vancomycin prescribing. RESULTS: There was a high prevalence of colonization with vancomycin-resistant enterococci among pediatric oncology patients. The length of hospitalization and the administration of vancomycin and other intravenous antibiotics was associated with colonization. Prevention of colonization was associated with restriction of vancomycin use and contact isolation. CONCLUSIONS: Vancomycin use may predispose to colonization with vancomycin-resistant E faecium. Vancomycin-resistant E faecium may be nosocomially spread. Contact isolation and restriction of vancomycin use may prevent spread of vancomycin-resistant E faecium.

Bacterial Typing Techniques↗
PubMed1992

Detection of autoimmunity parameters in the acquired immunodeficiency syndrome (AIDS).

We have examined various autoimmunity parameters in AIDS with special emphasis on the expression of pemphigus and bullous pemphigoid antibodies. Sera from healthy seropositive individuals without syphilis (CS-, n = 17), seropositive individuals with syphilis (cs+, n = 11), and patients with AIDS (n = 6) were studied and compared with normal controls (n = 30); autoimmunity parameters related to dermatology were evaluated. Indirect immunofluorescence (IIF) for pemphigus and pemphigoid antibodies, antinuclear antibodies (ANA), anti-DNA antibodies, antismooth muscle antibodies (ASMA) antimitochondrial antibodies (AMA), and antithyroid antibodies (ATA) was carried out and findings were graded with a cumulative index (CI) for each patient group. Pemphigus and bullous pemphigoid-like antibodies (IgG, PV + BP) were detected in 33% of the AIDS patients. Statistically increased CI (P less than 0.01) was found in the CS- group compared with the CS+ group and in the AIDS group compared with CS- (P less than 0.01).

Acquired Immunodeficiency Syndrome↗
PubMed1992

Tuberculosis associated hemophagocytic syndrome complicated with severe bone marrow failure and disseminated intravascular coagulation.

Tuberculosis associated hemophagocytic syndrome (HPS) has recently been recognized as a benign reactive histiocytic proliferation with marrow hemophagocytosis. To our knowledge, only five autopsy documented cases have previously been reported. We present here a unique case of the disorder complicated by severe bone marrow failure and disseminated intravascular coagulation. The possible mechanisms of these complications are discussed and it is concluded that the immunological disturbances usually occurring in miliary tuberculosis could play a role in the pathogenesis of HPS.

Aged↗
PubMed1991

The effect of recombinant alpha-interferon on natural killer cell activity and clinical course in patients with myelodysplastic syndrome.

Thirteen patients with myelodysplastic syndrome (MDS) were included in this study and consented to treatment with recombinant alpha-interferon (a-IFN). These patients were subclassified: six as RAEB, one as RAEB-T and six as CMML. T-cell subsets and natural killer cells were identified in the peripheral blood with the use of monoclonal antibodies and natural killer cell activity (NKa) was assayed before, during and after a-INF treatment. The treatment schedule consisted of 2.0 MU/m2 sc t.i.w. continuously for the three months. Prior to treatment, NKa was found decreased in 11 of 13 patients as compared to that of normal individuals. Following a-IFN administration, a rise of NKa was observed in eight of the eleven patients. In those who responded, a-IFN was continued for 1 to 21 months. Alpha-IFN treatment was myelosuppressive for most of the patients, but transient increase of the number of neutrophils and platelets was observed in 3 and of the reticulocytes in one patient. Disease progression was recorded in 9/13 patients (69%) at a median time of 17.3 months. The median overall survival was 30.5 months (range 7.5 to 65+ months). No evidence of a relationship was found between the rise in Nka and the limited clinical improvement observed. Two NKa responders under continuous a-IFN treatment are in stable clinical condition for 36+ and 65+ months. The study provides only limited evidence that a-IFN may improve the clinical course of patients with MDS.

Aged↗
PubMed1991

Impaired production of GM-CSA in bone marrow and peripheral blood monocytes in two patients with severe congenital neutropenia.

The capacity of bone marrow and peripheral blood cells to stimulate colony formation by normal granulocyte-macrophage progenitor cells (CFU-GM) was investigated in two patients with severe congenital neutropenia using soft agar-gel culture techniques. In both patients, monocyte/macrophage-derived colony stimulating activity (GM-CSA) in conditioned medium was found to be significantly decreased compared to the control. Furthermore, the capacity of patients' unfractionated peripheral blood leukocytes to stimulate normal CFU-GM in overlayers, was also found significantly decreased. In contrast, the number of bone marrow and peripheral blood CFU-GM was within the normal range in both patients. Patients' CFU-GM showed a normal pattern of in vitro differentiation when they were stimulated by exogenous GM-CSA. These data indicate that in some cases of severe congenital neutropenia, monocyte/macrophage-derived GM-CSA may be impaired. Whether this abnormality plays some role in the regulation of granulopoiesis in these patients is unclear.

Agranulocytosis↗
PubMed1991

Effect of recombinant alpha-interferon administration on peripheral blood lymphocyte subpopulations and natural killer cell activity in patients with refractory anemia with excess of blasts.

Peripheral blood lymphocyte subpopulations and natural killer cell activity (NKa) were determined in 7 patients with refractory anemia with excess of blasts (RAEB) subjected to alpha-interferon (alpha-IFN) administration. Patients received subcutaneously 3 MU alpha-IFN three times a week for 3 consecutive months, and studies were done just before and one month after the cessation of alpha-IFN administration. Before starting alpha-IFN, the patients NKa was severely reduced in relation to control (p less than 0.001), natural killer (NK) cells (CD16+ cells) and suppressor/cytolytic T-lymphocytes (CD8+ cells) were within normal range, while helper/inducer T-lymphocytes (CD4+ cells), as well CD4+/CD8+ cell ratio, were significantly reduced (p less than 0.001 and p less than 0.001, respectively). Significant diminution was also noted in B-lymphocyte numbers (CD19+ cells) (p less than 0.05). Following alpha-IFN administration, NKa values increased significantly in comparison to pre-IFN values (p less than 0.05), but failed to reach normal range. CD3+ cells and CD8+ cells decreased (p less than 0.05 and p less than 0.02), while CD4+ cells and CD4+/CD8+ cell ratio did not change significantly. A statistically significant rise was observed in CD16+ cells (p less than 0.05). The sensitivity of NK-cells against alpha-IFN and interleukin-2 (IL-2) added in vitro, was also significantly increased (p less than 0.05). The findings indicate that alpha-IFN administration may affect some disturbed immunologic functions in patients with RAEB, but further studies are needed to elucidate the mechanism and the extent of this action.

Aged↗
PubMed1990

Pseudallescheria boydii infection of the central nervous system.

Pseudallescheria boydii is a rare cause of central nervous system infection characteristically presenting as a neutrophilic meningitis or multiple brain abscesses. Factors predisposing to central nervous system infection with this fungus include immunosuppression and near drowning. The organism is infrequently cultured from fluid obtained by lumbar puncture, delaying clinical recognition and appropriate antifungal therapy. All untreated patients with P boydii infection of the central nervous system died. We describe a patient who developed a persistent neutrophilic meningitis with focal neurologic deficits due to P boydii 6 months after a freshwater aspiration pneumonia. We also review the characteristic clinical and pathologic features of previously reported cases and emphasize the importance of early detection and treatment in the management of this frequently intractable disease.

Adult↗