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Biomedical subjects

Julio Delgado

Publications and source records attributed to Julio Delgado.

16 recordsLinked to original sources
PubMed2004

Safety of the new selective cyclooxygenase type 2 inhibitors rofecoxib and celecoxib in patients with anaphylactoid reactions to nonsteroidal anti-inflammatory drugs.

BACKGROUND: Controlled oral challenge with nonsteroidal anti-inflammatory drugs (NSAIDs) is the only definite way to detect safe NSAIDs in patients with NSAID-induced anaphylactoid reactions. OBJECTIVE: To evaluate the safety of the selective cyclooxygenase (COX) type 2 inhibitors rofecoxib and celecoxib in patients with single-reactive, NSAID-induced anaphylactoid reactions. METHODS: We prospectively conducted single-blind, placebo-controlled oral challenges (SBPCOCs) with rofecoxib and celecoxib in 33 patients with single-reactive, NSAID-induced anaphylactoid reactions. RESULTS: Nineteen women and 14 men (age range, 20-78 years; mean age, 44.8 years) exhibited anaphylactoid reactions on emergency department admission. Symptoms involved the skin (100%), laryngeal edema (73%), systolic hypotension (39%), and the gastrointestinal system (15%). The NSAIDs most frequently involved in the episodes were dipyrone (64%), propyphenazone (12%), and diclofenac (12%). In all patients, tolerance to a potent, nondiscriminatory COX inhibitor (except those reported as being responsible for the reaction) was noted. The SBPCOCs with the selective COX-2 inhibitors celecoxib and rofecoxib were well tolerated in all cases. Twenty-three patients who had an anaphylactoid reaction involving dipyrone and propyphenazone showed good tolerance to celecoxib (which contains a pyrazole group in its structure) on challenge. CONCLUSIONS: The SBPCOCs with highly selective COX-2 inhibitors were safe in patients with single-reactive, NSAID-induced anaphylactoid reactions, even in cases that involved pyrazole derivatives.

Adult↗
PubMed2004

The diagnostic value of CD123 in B-cell disorders with hairy or villous lymphocytes.

BACKGROUND AND OBJECTIVES: CD123 is an antibody that identifies the a chain of the human interleukin-3 receptor and is expressed in a variety of normal hematopoietic cells, acute leukemia and hairy cell leukemia (HCL). The aim of the study was to investigate the diagnostic value of CD123 expression in B-cell disorders with circulating hairy and villous lymphocytes. DESIGN AND METHODS: We investigated the diagnostic value of CD123 expression in neoplastic cells from 59 patients with B-cell disorders with circulating hairy or villous lymphocytes: HCL (n=24), the variant form of HCL (n=11) and splenic lymphoma with villous lymphocytes (SLVL) (n=24). Cells from 12 patients with chronic lymphocytic leukemia were used as controls. Immunophenotypic analysis was performed by flow cytometry on 77 samples from peripheral blood (n=48), bone marrow (n=25) and spleen cell suspensions (n=4). RESULTS: Our findings show that cells from 95% of typical HCL express CD123 with strong to moderate intensity while this molecule is absent in circulating cells from most cases of HCL-variant (91%) and SLVL (97%). INTERPRETATION AND CONCLUSIONS: We conclude that CD123 is a useful new marker for distinguishing B-cell disorders with circulating villous lymphocytes as its expression is characteristic of typical HCL with high sensitivity and specificity. However CD123 does not allow the distinction between HCL-variant and SLVL, as both are CD123 negative.

Antibodies, Monoclonal↗
PubMed2003

Photogeneration of o-quinone methides from o-cycloalkenylphenols.

6-Alkylidenecyclohexa-2,4-dienones (o-quinone methides II) have been generated by photolysis of 2-(2'-cycloalkenyl)phenols 1 and trapped by methanol to give the ring-opened products 2. The best results have been obtained with the cyclohexenyl derivatives 1a, 1e, and 1f. In the case of the cyclopentenyl derivative 1b, photoproduct 2b was not observed, whereas only small amounts of 2c and 2d were formed from the seven- and eight-membered ring analogues 1c and 1d. Thus, ring size appears to be a key factor in the formation of o-quinone methides. This experimental result has been rationalized by means of density-functional theory (DFT) calculations. On the other hand, phenol substitution also appears to play a role in the process. Thus, electron-withdrawing groups such as CF(3) (1f) accelerate the reaction, whereas the opposite is true for electron-donating groups such as OCH(3) (1e). This is explained by an excited-state intramolecular proton transfer (ESIPT) mechanism, as the above results are consistent with the excited-state acidities of the different phenols. The lack of reactivity in the case of ketone 1g, where the intersystem crossing quantum yield is close to unity, allows us to rule out a mechanism involving the triplet state.

Journal Article↗
PubMed2003

Silencing of the p18INK4c gene by promoter hypermethylation in Reed-Sternberg cells in Hodgkin lymphomas.

p18INK4c is a cyclin-dependent kinase (CDK) inhibitor that interferes with the Rb-kinase activity of CDK6/CDK4. Disruption of p18INK4c in mice impairs B-cell terminal differentiation and confers increased susceptibility to tumor development; however, alterations of p18INK4c in human tumors have rarely been described. We used a tissue-microarray approach to analyze p18INK4c expression in 316 Hodgkin lymphomas (HLs). Nearly half of the HL cases showed absence of p18INK4c protein expression by Reed-Sternberg (RS) cells, in contrast with the regular expression of p18INK4c in normal germinal center cells. To investigate the cause of p18INK4c repression in RS cells, the methylation status of the p18INK4c promoter was analyzed by methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing. Hypermethylation of the p18INK4c promoter was detected in 2 of 4 HL-derived cell lines, but in none of 7 non-Hodgkin lymphoma (NHL)-derived cell lines. We also detected p18INK4c hypermethylation, associated with absence of protein expression, in 5 of 26 HL tumors. The correlation of p18INK4c immunostaining with the follow-up of the patients showed shorter overall survival in negative cases, independent of the International Prognostic Score. These findings suggest that p18INK4c may function as a tumor suppressor gene in HL, and its inactivation may contribute to the cell cycle deregulation and defective terminal differentiation characteristic of the RS cells.

Cell Cycle Proteins↗
PubMed2003

Diagnostic significance of CD20 and FMC7 expression in B-cell disorders.

We analyzed by flow cytometry the expression of CD20 and FMC7 in cell suspensions from 932 patients, including 630 cases of chronic lymphocytic leukemia (CLL), 23 cases of other B-cell leukemias, and 279 cases of B-cell non-Hodgkin lymphoma (B-cell NHL). CD20 was positive in 94.5% of cases; FMC7 was positive in 35.7%. There was a correlation between CD20 and FMC7 expression in patients with B-cell NHL (P < .001) but not CLL (P = .1). We also tested a scoring system in which FMC7 was replaced by CD20 and compared it with our current scoring system for CLL. With this modification, the accuracy of the scoring system for differentiating CLL from other non-CLL disorders fell from 94.4% to 81.5%. In CD20+ CLL, the intensity of CD20 expression correlated with FMC7 and low scores (P < .001 for both comparisons). We suggest that the particular conformation of CD20 recognized by FMC7 is manifested only in cells with strong CD20 expression, which is not the case for CLL. FMC7 is of greater diagnostic value than CD20 for distinguishing CLL from other B-cell disorders; we recommend its continued use for this purpose.

Antigens, CD20↗
PubMed2002

CD56 expression in myeloperoxidase-negative FAB M5 acute myeloid leukemia.

CD56 is a natural killer (NK) cell marker that has been identified in approximately 15-20% of acute myeloid leukemia (AML) cases, where it has been associated with monocytic morphology and chromosomal abnormalities such as trisomy 8, t(8;21), t(15;17), and 11q23 rearrangements. The clinical presentation, chromosomal abnormalities as detected by fluorescent in-situ hybridization (FISH), and clinical outcomes of 7 patients with AML are presented. These cases were characterized by French-American-British (FAB) M5 morphology, myeloperoxidase (MPO) negativity, and co-expression of myelomonocytic and NK cell-associated antigens (CD11c(+), CD13(+), CD15(+), CD33(+), HLA-DR(+), and CD56(+)). All patients presented lymph node, hepatic, or splenic involvement at diagnosis. Despite the homogeneous morphologic and immunophenotypic characteristics the outcomes varied considerably. Two patients died during induction therapy, but the other five patients attained complete remission (CR). Of these five patients, 4 have received a bone marrow transplantation (autologous or allogeneic) and 3 of them are in CR (median follow-up: 45 months). The three patients with 11q23 rearrangements had a poor outcome and died of their disease within 1 year of diagnosis. Further studies with a larger group of patients would help establish the actual prognostic value of these morphologic, immunophenotypic and cytogenetic features.

Adolescent↗
PubMed2002

Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone as treatment of Bing-Neel syndrome: Case report and review of the literature.

Waldenström's macroglobulinemia is a low-grade lymphoma that produces monoclonal IgM. Central nervous system symptoms are frequent in Waldenström's macroglobulinemia, mostly associated with blood hyperviscosity. Nevertheless, central nervous system infiltration by malignant cells (Bing-Neel syndrome) has rarely been reported. We describe the case of a 72-year-old man with Waldenstrom's macroglobulinemia and central nervous system infiltration by malignant cells with tumor formation. All similar cases reported in the literature are reviewed and the different therapeutic approaches discussed.

Aged↗
PubMed2002

Acquired hemophilia: a single-center survey with emphasis on immunotherapy and treatment-related side-effects.

OBJECTIVES: Acquired hemophilia is a rare disease caused by the development of autoantibodies against factor VIII. Since 1981 we have observed 17 patients with this disorder in our institution. The objective of this survey was to assess the epidemiological features, clinical course, and mortality rate of these patients, with special emphasis on therapy-related side-effects. Also, we present our results with an immunosuppressive approach based on the severity of bleeding episodes. METHODS: Clinical records of all patients with acquired hemophilia due to factor VIII inhibitor admitted or referred to our hospital between 1981 and 2001 were reviewed retrospectively. We collected each patient's sex, age, medical history, presenting symptoms, activated partial thromboplastin time, factor VIII activity, and inhibitor titre. Patient's clinical courses, including their bleeding episodes, response to therapy, and therapy-related side-effects, were also recorded. RESULTS: Complete and partial responses were achieved in 14 and one patient, respectively (overall response rate 88%) after a median time to complete response of 3.5 months (range 30 d - 25 months). The inhibitor-related and overall mortality rates were 12% and 29%, respectively. Side-effects were frequent: two patients had blood-borne infections, three patients had thrombotic complications, and nine patients had immunosuppressive therapy-related side-effects. In five patients, discontinuation of cyclophosphamide or prednisone was required. CONCLUSIONS: Although our response rates were remarkable, this survey showed that treatment-related morbidity could also be very important. Therefore, it is pertinent to bear in mind these potential side-effects in order to decide the most appropriate therapy for each particular patient.

Adult↗
PubMed2002

Are activation markers (CD25, CD38 and CD103) predictive of sensitivity to purine analogues in patients with T-cell prolymphocytic leukemia and other lymphoproliferative disorders?

T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoproliferative disorder with distinctive clinical and laboratory features. It is often resistant to conventional chemotherapy, but complete or partial responses have been documented with the use of purine analogues. We report on two cases of T-PLL with a slightly different immunophenotype but a remarkably different response to pentostatin. We discuss the possible therapeutic implications of this finding and establish a comparison between immunophenotype and sensitivity to purine analogues in patients with T-PLL and other chronic lymphoproliferative disorders.

ADP-ribosyl Cyclase↗
PubMed2002

Anti-CD20 monoclonal antibody therapy in refractory immune thrombocytopenic purpura.

Multiple agents have been tried in patients with refractory immune thrombocytopenic purpura (ITP); however, none of these stands as a clear first choice. We administered rituximab, 375 mg/m2 weekly x 4, to four patients with refractory ITP. With a median follow-up of 7 months, one patient has achieved a complete response, proving the possible efficacy of such a therapeutic modality in this context.

Adult↗
PubMed1999

Photoreactions of trans-1-o-Hydroxyphenyl-2-phenylcyclopropane.

The photochemistry of trans-1-o-hydroxyphenyl-2-phenylcyclopropane, trans-1, was studied under a variety of experimental conditions. Direct irradiation through quartz in cyclohexane gave rise mainly to ring-expanded products, 2-phenyl-3,4-dihydro-2H-benzopyran, 2, 2-benzyl-2,3-dihydrobenzofuran, 3, and 1-o-hydroxyphenylindan, 4. The major products, 2 and 3, are rationalized by intramolecular proton transfer. However, a significant fraction of 3 is formed via ring-opening to cinnamylphenol, 5. An additional product, o-(alpha-cyclohexylmethyl)phenol, 7, suggests fragmentation of trans-1 and (formal) insertion of o-hydroxyphenylcarbene into cyclohexane. Direct irradiation in methanol produced methanol adducts 8 and 9 instead of 2, 3, 4, or 7. Finally, acetone-sensitized irradiation of trans-1 resulted in geometric isomerization to cis-1; this result can be rationalized via a biradical intermediate.

Journal Article↗