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Biomedical subjects

E Granados

Publications and source records attributed to E Granados.

At least 19 recordsLinked to original sources
PubMed2006

High-brightness injection-seeded soft-x-ray-laser amplifier using a solid target.

We demonstrate the generation of an intense soft-x-ray-laser beam by saturated amplification of high harmonic seed pulses in a dense transient collisional soft-x-ray-laser plasma amplifier created by heating a titanium target. Amplification in the 32.6 nm line of Ne-like Ti generates laser pulses of subpicosecond duration that are measured to approach full spatial coherence. The peak spectral brightness is estimated to be approximately 2 x 10(26) photons/(s mm(2) mrad(2) 0.01% bandwidth). The scheme is scalable to produce extremely bright lasers at very short wavelengths with full temporal and spatial coherence.

Journal Article↗
PubMed2001

High expression of the ILT2 (LIR-1) inhibitory receptor for major histocompatibility complex class I molecules on clonal expansions of T large granular lymphocytes in asymptomatic patients.

BACKGROUND AND OBJECTIVES: The lymphoproliferative disorders of large granular lymphocytes (LGLD) are divided into two groups: T-cell type and NK-cell type. These entities may be either asymptomatic or associated with autoimmune manifestations (especially cytopenias). A number of surface receptors, expressed by NK-cells and some T-lymphocyte subsets repress cytotoxicity and cytokine production upon ligation with HLA class I molecules and are clonally expressed in theses lymphoproliferative disorders. These cytotoxic lymphocytes can lyse erythroid progenitors in vitro, and the physiologic lower levels of HLA class I antigens on the erythroid lineage may contribute to this form of autoimmunity. It is conceivable that the clinical outcome of T-LGLD might be influenced by the expression of MHC class I inhibitory receptors. DESIGN AND METHODS: We analyzed the surface expression of these molecules, lectin-like heterodimers (CD94/NKG2A) or killer immunoglobulin (Ig)-like receptors (KIR) and another Ig-like inhibitory receptor, termed ILT2 or LIR-1 in CD8+ cells from 12 cases of ab T-LGLD using specific monoclonal antibodies. RESULTS: None of the LGLD cases had anemia and 11 of 12 patients remain asymptomatic. KIR and CD94/NKG2A expression was detected on CD8+ populations only in some cases of T-LGLD. By contrast, our observations revealed that ILT2 expression was markedly higher in CD8+ cells from LGLD patients than from healthy donors. INTERPRETATION AND CONCLUSIONS: Expression of the ILT2 inhibitory receptor for HLA class I molecules on LGLD cells might indeed contribute to preventing their autoreactivity. Further studies are required to evaluate the expression/function of the ILT2 receptor in patients who eventually become symptomatic. The development of cytopenias in LGLD patients must involve other self-reactive activating receptors. Analysis of the expression and function of triggering NKR in LGLD needs to be carefully addressed.

Adult↗
PubMed2000

Tuberculosis after hematopoietic stem cell transplantation: incidence, clinical characteristics and outcome. Spanish Group on Infectious Complications in Hematopoietic Transplantation.

A national survey of tuberculosis after hematopoietic stem cell transplant (SCT) was undertaken to study incidence, clinical presentation and outcome. Twenty confirmed cases were found among 8,013 patients (eight in 5,147 autologous and 12 in 2,866 allogeneic SCT). The estimated incidence in cases/10(5) patients/year (95% CI) was 101 (56.5-145) for the whole group, 71.1 (21.8-120) in autologous and 135.6 (58.9-212) in allogeneic transplants. Compared with the general population, tuberculosis was more frequent after allogeneic (RR 2.95) but not after autologous SCT. Tuberculosis after SCT is a late infection (median 324 days post transplant), predominately affects the lungs (80% of the cases), appears to respond well to treatment but has a high mortality (25%) in allogeneic recipients. It can also complicate the post-transplant management as antituberculosis drugs frequently decrease the serum levels of cyclosporine causing an aggravation of GVHD. Graft-versus-host disease, corticosteroid treatment and total body irradiation appear to be associated with tuberculosis in allogeneic recipients. No obvious factors were associated with tuberculosis in autologous transplants. Finally, we found that the published literature on tuberculosis after solid and SCT has overestimated its incidence due to the direct translation of tuberculosis frequency into incidence.

Adult↗
PubMed2000

Hematopoietic cell transplantation in acute lymphoblastic leukemia: better long term event-free survival with conditioning regimens containing total body irradiation.

BACKGROUND AND OBJECTIVES: There is only limited experience with conditioning regimens based on busulfan for patients with acute lymphoblastic leukemia (ALL). Therefore, the aim of this study was to compare the event-free survival (EFS), transplant-related mortality (TRM) and the probability of relapse (PR) of patients undergoing hematopoietic cell transplantation (HCT) for ALL conditioned with or without total body irradiation (TBI). DESIGN AND METHODS: The study sample consisted of 156 patients conditioned with regimens based on TBI (n=114) or on high doses of oral busulfan (BU) (n=42). Most of the BU group received phenytoin as prophylaxis for seizures. The median follow-up was 6 years. RESULTS: EFS at 6 years was 43% (95% CI 35%-51%) versus 22% (95% CI 10%-34%) in the TBI and BU subsets respectively (p=0.01). TRM at 18 months was 22% and 17% in the BU and TBI groups (p=0.24), respectively. At 3 years actuarial PR was 71% in the BU group and 47% in the TBI group (p=0.01). In the multivariable analysis, a worse EFS was associated with BU, relative risk (RR) 1.7; advanced disease versus 1st and 2nd complete remission (CR) at HCT, RR 2.5; absence of chronic graft-versus-host disease, RR 1.8; development of veno-occlusive disease RR 2.2 and shorter CR duration before transplant. INTERPRETATION AND CONCLUSIONS. TBI was associated with a lower relapse rate and better EFS, even in patients in 1(st )and 2(nd) CR, than schemes based on high doses of busulfan. This suggests that conditioning regimens based on TBI should remain the standard method of preparative regimen for patients with ALL.

Adolescent↗
PubMed1999

Interferon alpha for chronic myeloid leukemia relapsing after allogeneic bone marrow transplantation.

Interferon alpha (IFN alpha) induces cytogenetic responses in patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT). The purpose of this study was to analyze the therapeutic role of IFN alpha in this setting. The experience of a single institution and the published results on this topic were evaluated. We have included patients who received IFN alpha as a single agent, excluding those patients who received previous or simultaneous donor leukocyte infusions. The outcomes of 11 patients treated in our center and those of 108 previously reported patients have been analyzed. Five out of 11 patients treated in our institution obtained a complete cytogenetic response (CGR). Two patients continue in complete cytogenetic response 3.5 and 8.2 years later, and the qualitative RT-PCR is negative for bcr-abl RNA. The CGR has been transient in one patient, and follow-up is short in the other two. Secondary effects have been acceptable, with myelosuppression as the main toxic effect. Graft-versus-host disease did not occur. The literature review identified 108 patients treated with IFN alpha as sole therapy for relapsed CML. Cytogenetic response and CGR seem to be better in patients with cytogenetic relapse, as compared to patients with hematologic relapse (61% vs. 45% and 45% vs. 28%, respectively). Several patients remained in CGR for more than 5 years. This overview also suggests that CGR is more frequent when IFN alpha is used in patients relapsing after non T-depleted BMT. IFN alpha induces complete cytogenetic response in nearly half of the patients with CML who relapse after allogeneic BMT, with acceptable toxicity. We believe that these results using IFN alpha as a front-line therapy for CML relapsing after BMT warrant a randomized comparison with donor lymphocyte infusions.

Antineoplastic Agents↗
PubMed1999

Long-term management of homozygous protein C deficiency: replacement therapy with subcutaneous purified protein C concentrate.

We present the case of a full-term newborn in whom purpura fulminans developed shortly after birth. A diagnosis of homozygous protein C deficiency was established based upon undetectable plasma protein C activity and antigenemia in the newborn infant, and was later confirmed by protein C gene analysis. Specific replacement therapy with intravenous protein C concentrate was started 9 days after birth. This rapidly led to the complete regression of cutaneous lesions and consumption coagulopathy. After stabilization, oral anticoagulation was initiated in association with prophylactic treatment with intravenous protein C concentrate. However, oral anticoagulation was finally abandoned as the patient presented several thrombotic and hemorrhagic episodes clearly related to difficulties with anticoagulation. Due to the hazards related to prolonged venous access, we are currently using subcutaneous infusion of protein C concentrate for the long-term management of this condition, with satisfactory results.

Administration, Oral↗
PubMed1998

Severe autoimmune hepatitis in a chronic myeloid leukemia patient treated with interferon alpha and with complete genetic response.

A patient with chronic myeloid leukemia (CML) treated with interferon alpha (IFN alpha) and who developed autoimmune hepatitis (AIH) is described. The patient was treated with IFN alpha 2a, a complete cytogenetic response was achieved 5 months later, and this response has lasted now more than 7 years. Autoimmune hypothyroidism appeared at 18 months of treatment, and 1 year later severe type I autoimmune hepatitis developed. To our knowledge this is the first report of such complication in an IFN alpha-treated CML patient.

Autoimmune Diseases↗
PubMed1998

Autologous stem cell transplantation (ASCT) for poor prognostic Hodgkin's disease (HD): comparative results with two CBV regimens and importance of disease status at transplant.

Clinical outcome of 47 consecutive patients with advanced HD who underwent ASCT in our Department was analyzed retrospectively. Median age was 28 years (28 males and 19 females). At transplant, 15 (32%) patients were in CR (five in first CR after two chemotherapy regimens and 10 in second CR), eight (17%) in PR (seven without a prior CR), 22 (51%) had relapsing disease (19 with sensitive relapse) and two had primary refractory disease. The CVB regimen with two different schedules was used: 22 (47%) patients received standard CBV (CY 6 g/m2, BCNU 300 mg/m2 and etoposide 600 mg/m2) and 25 (53%) received an increased CBV dose (CY 7.2 g/m2, BCNU 440 mg/m2 and etoposide 2 g/m2). Antitumor response for 28 evaluable patients was similar for both CBV regimens: 87 and 75% (P=0.39). At 7.2 years, actuarial overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole series were 51.7+/-8%, 34+/-9% and 28+/-8%, with a median follow-up for the surviving patients of 3 years (0.7-7.6). No differences in these survival functions according to the CBV regimen used were observed (P=0.57). A history of a prior CR (P=0.003), duration of first CR >1 year (P=0.04), absence of bulky nodal disease at transplant (P=0.054), absence of extranodal disease at transplant (P=0.01), and a CR status at transplant (P=0.0006) were associated with a better PFS on univariant analysis. On multivariate analysis, only CR status at transplant remained significant (P=0.05). When patients in second CR at transplant and those in first sensitive relapse were analyzed separately, no differences in clinical characteristics or in treatment received pretransplant were observed; however, PFS was significantly different (P=0.01). In conclusion, CR status at transplant is useful in identifying 'good risk' patients and is necessary to obtain the greatest benefit from ASCT independent of the CBV regimen used.

Adolescent↗
PubMed1998

Persistent polyclonal B lymphocytosis with multiple bcl-2/IgH rearrangements: a benign disorder.

The appearance of a chronic B lymphocytosis is usually associated with the existence of an underlying monoclonal malignant condition. However, a few cases of persistent polyclonal B cell lymphocytosis (PPBL), presented in young asymptomatic women with an uneventful course, have been reported in recent years. In these PPBL cases, since the lymphocytes usually display an anomalous morphology, a false diagnosis of a neoplastic chronic lymphoproliferative syndrome can be easily made. We report a typical case of PPBL that presents multiple bcl-2 rearrangements, the typical finding of follicular lymphomas. A review of different causes of benign non neoplastic lymphocytosis with special steadiness in changes in the lymphoid subsets will be made.

Adult↗
PubMed1998

[Treatment with lymphoblastoid alpha interferon in patients with chronic myeloid leukemia refractory to recombinant interferon alpha 2].

The results of the treatment with lymphoblastoid alpha interferon (IFN-alpha N1) in 10 patients with chronic myeloid leukaemia who had poor response to previous recombinant alpha interferon (rIFN-alpha) are presented. Eight of these patients had not developed anti-alpha 2 interferon antibodies, and 2 had non-neutralising anti-IFN antibodies. Three of the 10 patients received benefit from IFN-alpha N1 treatment. Two of them, with no response to rIFN alpha 2, attained complete haematologic response wit IFN-alpha N1. Cytogenetic responses although minimal, were achieved as well. The third patient, after receiving rIFN-alpha for 3 years with no response, had partial cytogenetic response after 4 months of treatment with IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN alpha 2 without anti-IFn alpha 2 neutralising antibodies may be useful in a minority of patients, although the frequency of cytogenetic responses is low.

Adult↗
PubMed1996

Quinton-Mahurkar catheter as short-term central venous access for PBSC collection: single-center experience of 370 aphereses in 110 patients.

We retrospectively analyzed our experience with the Quinton-Mahurkar dual-lumen hemodialysis catheter as short-term central venous access for harvesting peripheral blood stem cells (PBSC) for autologous transplantation. For intensification therapy for various malignancies 370 leukaphereses were performed in 110 candidates. The catheter was placed percutaneously under local anesthesia only for the time of blood collection and in no case was it used for the PBSC transplant. No systemic antithrombotic prophylaxis was administered. PBSC were collected using a continuous flow cell separator, COBE Spectra, after mobilization with chemotherapy followed by cytokine: rhGM-CSF and rhG-CSF s.c. (35 patients) or rhG-CSF s.c. alone (75 patients). The median number of aphereses was two (1-13). Eighty-nine patients (81.3%) required three or fewer sessions to collect the minimum mononuclear cell target number of 6 x 10(8) MNC/kg. The volume of blood per kg body weight processed for each apheresis was 240 ml (range 150-560 ml) equivalent to 13 l (6-30 l) and the median flow rate was 61 ml/min (range 30-90 ml/min). The total CD34+ cell yield per patient was 3.55 x 10(6)/kg (0.26-34.8) and the MNC yield was 6.1 x 10(8)/kg (2.96-12.6). We observed the following complications: local infection in four cases (3.6%), catheter occlusion for local thrombosis in two cases (1.8%) and pneumothorax in one case (0.97%). In our experience the Mahurkar-Quinton catheter, when placed specifically for apheresis sessions, was very effective and safe for PBSC harvesting with a low incidence of complications.

Catheterization, Central Venous↗
PubMed1985

Purification of carboxymethylcellulose decreases toxicity of poly ICLC in mice.

The interferon inducer poly ICLC has toxic side effects; the carboxymethylcellulose (CMC) component is a possible source of this toxicity. We have purified CMC by ethanol extraction, and found that poly ICLC made with purified CMC is not significantly different in its effectiveness as an interferon inducer in mice than poly ICLC made with unpurified CMC, but is less toxic.

Animals↗
PubMed1982

Conformation and aggregation of melittin: dependence on pH and concentration.

Melittin, a 26-residue peptide from bee venom, is transformed from a largely random to a largely alpha-helical conformation at elevated pH. At 3 x 10(-5) M melittin, circular dichroism spectra show a transition with a pK near 9.6. At 8 x 10(-5) M, two approximately equal transitions occur with pKs at 7.2 and 9.6. At 6 x 10(-4) M, a single transition is seen with a pK of 6.8, followed by a more gradual increase to at least pH 11. The transitions near pH 7 presumably arise from deprotonation of the alpha-amino group. When the amino groups are acetylated or succinylated, a 60% alpha-helical conformation is adopted at neutral or low pH. The acylated melittins form more stable oligomers than does native melittin.

Bee Venoms↗