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Biomedical subjects

Julio Delgado

Publications and source records attributed to Julio Delgado.

At least 19 recordsLinked to original sources
PubMed2006

The effect of immunoglobulin VH gene mutation status and other prognostic factors on the incidence of major infections in patients with chronic lymphocytic leukemia.

BACKGROUND: Infections are a major factor in the clinical course of chronic lymphocytic leukemia (CLL) and account for 30% to 50% of all deaths. The pathogenesis of infections in CLL is related to hypo-gamma-globulinemia, T-cell immune dysfunction, and the immunosuppressive effect of treatment. METHODS: The authors retrospectively assessed the correlations between new prognostic markers and types of infections encountered, the time taken to develop these infections, and infection-related mortality in 280 unselected patients with CLL. RESULTS: One hundred patients (36%) had at least 1 major infection (median, 2 major infections; range, 1-8 major infections) over a median follow-up of 67 months. Infections were the most common cause of death, accounting for 51% of all fatalities. Older age (P = .007), clinical Stage B or C disease (P < .001), unmutated immunoglobulin (Ig)VH gene status (P < .001), genetic abnormalities (P < .001), positive CD38 status (P < .001), and type of initial therapy were associated with a significantly shorter time to first infection. Equally, patient age (P < .001), disease stage (P < .001), CD38 expression (P < .001), IgVH mutation status (P < .001), and genetic abnormalities (P = .003) had a significant impact on infection-related mortality. CONCLUSIONS: Clinical stage at diagnosis, IgVH mutation status, and initial therapy were possible predictors of severe infections in patients with CLL. The current results may help to identify which patients with CLL are at particularly high risk of developing serious infections and, thus, should be considered for Ig or antibiotic prophylaxis.

Adult↗
PubMed2006

Two germ line polymorphisms of the tumour suppressor gene p53 may influence the biology of chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is characterised by the accumulation of mature B lymphocytes. Defects in the tumour suppressor gene p53 pathway are known to be important in CLL and p53 inactivation is associated with a particularly aggressive form of CLL. A single nucleotide polymorphism (SNP) in codon 72 of TP53 leads to a single amino acid change leading to a change in apoptotic potential and alters prognosis in squamous carcinomas. A polymorphism within intron 6 of TP53 has been postulated to alter the susceptibility to lung cancer. Our study looked at the influence of these two polymorphisms in a cohort of approximately 200 CLL patients. The codon 72 polymorphism A2/A2 genotype (homozygous arginine) was associated with an increased susceptibility to CLL and CD38 negativity but did not appear to influence other biological behaviour or clinical response. The intron 6 polymorphism A2/A2 genotype was strongly associated with early stage disease, CD38 negativity and a longer time to first treatment. The effect on time to treatment did not retain significance in multivariate analysis and the polymorphism did not predict for overall survival (OS). Detailed investigation of the complete TP53 genotype is warranted to further characterise the role of SNPs in p53 and their influence on CLL.

Adult↗
PubMed2006

The importance of age, fludarabine, and total body irradiation in the incidence and severity of chronic renal failure after allogeneic hematopoietic cell transplantation.

Nonmalignant late effects, including chronic renal failure (CRF), impair the quality of life of long-term survivors after allogeneic hematopoietic cell transplantation. One of the major risk factors is the use of total body irradiation (TBI) in the preparative regimen; TBI is currently fractionated in an attempt to reduce toxicity. We analyzed 241 patients who had TBI-based preparative regimens for allogeneic hematopoietic cell transplantation. TBI was delivered as a single fraction of 7.5 Gy (7.5S group), 12 Gy in 6 fractions (12F group), or 14.4 Gy in 8 fractions (14.4F group). The cumulative incidence of CRF at 2 years was 12%. Statistical analysis revealed that older age (P < .001) and fludarabine administration (P = .016) had a significant effect on the incidence of CRF. Furthermore, single-fraction TBI was also significantly associated with CRF severity, because 7 (6.3%) of 111 patients in the 7.5S group developed severe CRF, as opposed to 1 (0.8%) of 130 patients in the 12F and 14.4F groups combined (P = .044). However, these conclusions should be regarded as preliminary in view of the retrospective and nonrandomized nature of this study.

Adolescent↗
PubMed2006

Vascularized bone blocks from the toe phalanx to solve complex intercalated defects in the fingers.

PURPOSE: Vascularized bone transplants resist infection and allow rapid healing but keeping small bony segments vascularized, as needed for a finger defect, is a challenge. The purpose of this article is to present a cohort of patients with traumatic intercalated compound bony defects in the fingers that were reconstructed by a vascularized toe phalanx (or part of a phalanx) in a single stage. METHODS: Eight patients were treated with an intercalary vascularized bone graft that included a part of the proximal phalanx (3 patients), most of the middle phalanx (4 patients), or a portion of each phalanx (1 patient) of a second toe (totaling 9 bone blocks). There was an associated soft-tissue defect in each patient, an infection in 6 patients, and cartilage loss in 4 patients. The toes were pedicled on the proper digital artery (6 patients) or a segment of the first dorsal metatarsal artery (2 patients). A mean length of 12 mm of vascularized bone was transferred. The associated skin island varied from a minimum of 2 x 1 cm to a maximum of 5 x 3 cm. Bleeding from all of the bone surfaces was evidenced once the clamps were released. The homolateral digital nerve and the contralateral neurovascular pedicle of the toe were kept in place. The toe defect was treated by soft-tissue arthroplasty or arthrodesis. No toe was amputated. RESULTS: Radiologic bony union was evident at 4 to 6 weeks, except in 1 patient with an acute infection whose distal union failed to unite at 6 weeks because the infection recurred. Finger length loss averaged 3 mm. All patients returned to their preoperative occupation. CONCLUSIONS: In this group of patients the toe phalanx reliably maintained its vascularization, allowing us to solve compound osteocutaneous defects in the fingers in a single stage. Donor site morbidity was minimal.

Adult↗
PubMed2006

The P2X7 receptor gene polymorphism 1513 A-->C has no effect on clinical prognostic markers and survival in multiple myeloma.

A P2X7 receptor gene polymorphism 1513 A-->C has recently been suggested as playing a role in the pathogenesis and disease progression of chronic lymphocytic leukemia, although several studies have failed to show any effect of the polymorphism. The effects of this polymorphism were analysed in 136 patients with multiple myeloma. The frequency of the polymorphism in the myeloma samples was not significantly different from that found in normal healthy controls. There was no significant difference in age at diagnosis, creatinine, hemoglobin, beta-2 microglobulin, immunoglobulin sub-type, duration of first response and overall survival. These results are in keeping with findings in a cohort of 121 chronic lymphocytic leukemia and do not support a role for this polymorphism in multiple myeloma.

Alleles↗
PubMed2005

Results of alemtuzumab-based reduced-intensity allogeneic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation Study.

We report results in 41 consecutive patients with chronic lymphocytic leukemia (CLL) who underwent allogeneic hematopoietic cell transplantation (HCT) after fludarabine, melphalan, and alemtuzumab conditioning. Donors were 24 HLA-matched siblings and 17 unrelated volunteers, 4 of them mismatched with recipients. All but 3 patients had initial hematologic recovery, but 5 more patients had secondary graft failure. Median intervals to neutrophil (greater than 0.5 x 10(9)/L) and platelet (greater than 20 x 10(9)/L) recovery were 14 days (range, 9-30 days) and 11 days (range, 8-45 days), respectively. Eleven (27%) patients had relapses and received escalated donor lymphocyte infusions, but only 3 of them had sustained responses. Acute and chronic graft-versus-host disease (GVHD) was observed in 17 (41%) and 13 (33%) patients, respectively. Seventeen (41%) patients have died, 5 of progressive disease. The 2-year overall survival and transplantation-related mortality (TRM) rates were 51% (95% confidence interval [CI], 33%-69%) and 26% (95% CI, 14%-46%), respectively. The alemtuzumabbased regimen was feasible and effective in patients with CLL with a relatively low rate of GVHD. However, TRM remains relatively high as a result of a variety of viral and fungal infections. Studies are ongoing to address the efficacy of reduced doses of alemtuzumab in this group of immunosuppressed patients.

Adult↗
PubMed2005

Gender dimorphism and altitudinal variation of secondary compounds in leaves of the gynodioecious shrub Daphne laureola.

In this article, we analyzed the concentration of coumarins in leaves of female and hermaphrodite individuals of the gynodioecious shrub Daphne laureola, along an elevational gradient in southern Spain. Combining HPLC and NMR techniques, we identified three different glycosides of 7-methoxycoumarin in leaves of this species. Total coumarin concentration averaged between 60 and 120 mg/g dry weight for mature summer leaves of D. laureola growing at six different populations. As predicted by optimal theory, females tended to have a higher concentration of coumarins than hermaphrodites, thus upholding the idea that male reproductive function is costly for hermaphrodites. Furthermore, concentrations in females but not hermaphrodites were positively correlated with increasing population altitude, and the magnitude of gender divergence in coumarin concentration varied among populations, suggesting that the cost of the male function may be context dependent. To our knowledge, this is the first evidence of gender differences in chemical defenses of a gynodioecious species in the field.

Altitude↗
PubMed2005

Histologic features of the liver biopsy predict the clinical outcome for patients with graft-versus-host disease of the liver.

We reviewed liver histologic results from all allogeneic hematopoietic stem cell transplant recipients from our institution with a confirmed diagnosis of liver graft-versus-host disease (L-GVHD), no concomitant causes of liver dysfunction, and at least 1 diagnostic liver biopsy sample (n=33) to ascertain whether histologic features predicted clinical outcome. The 1-year probability of nonrelapse mortality (NRM) from the onset of liver dysfunction was 68.15%, with a median overall survival (OS) of 6.2 months for the entire group. Histologic features traditionally linked to the diagnosis of L-GVHD (eg, bile duct damage, bile duct lymphocytic infiltration, portal inflammation, and ductopenia) had no association with patient outcome. However, an extended histologic analysis showed that a high level of lobular inflammation (LI) and a low level of hepatocyte ballooning (HB) were independent favorable prognostic factors for NRM (RR, 5.14; P=.033; and relative risk (RR), 0.18; P=.018, respectively) and OS (RR, 3.99; P=.032; and RR, 0.23; P=.037, respectively). The presence and severity of LI and HB were not associated with patient- or transplant-related characteristics or L-GVHD clinical factors such as timing of the biopsy from the onset of L-GVHD, acute versus chronic presentation, or whether the patients had started immunosuppressive treatment with steroids at the time of the biopsy. In multivariate analysis that included clinical prognostic factors, the combined histologic risk posed by high LI and low HB retained independent favorable prognostic value for NRM (RR, 5.05; P=.015) and OS (RR, 3.31; P=.038). This information, if replicated in other studies, could expand current indications for liver biopsy in patients with L-GVHD, not only to exclude other causes of liver injury, but also to predict clinical outcome, and should be considered in the selection of patients and the design of future trials with new experimental therapies for this complication. Prospective validation of our findings is warranted.

Adolescent↗
PubMed2005

Results of osteotomy, open reduction, and internal fixation for late-presenting malunited intra-articular fractures of the base of the middle phalanx.

PURPOSE: To present our results in the treatment of late-presenting impaction fractures of the base of the middle phalanx treated by osteotomy with full exposure of the articular surface to restore the normal anatomy. METHODS: Eleven patients with a malunited (impacted) fracture of the base of the middle phalanx were treated by osteotomy more than 5 weeks after the injury. All fractures had varying degrees of impaction, comminution, and dorsal subluxation. The malunited joint surface was visualized by dislocating the joint by hyperextension (shotgun approach). The restoration of the cup-shape contour of the middle phalangeal base was accomplished by osteotomy and mobilization of small osteochondral fragments. Rigid fixation was performed by cerclage wire, screws, or a combination of these. A distal radius bone graft was placed beneath disimpacted fragments in 9 of the 11 procedures. RESULTS: Ten of 11 patients were followed-up for more than than 1 year. One patient with a volar lateral impaction fracture was lost to follow-up study 4 weeks after the surgery and was excluded from the results. All patients except 1 achieved a functional range of motion of the proximal interphalangeal joint. Moderate limitations of the distal interphalangeal joint motion were common. Grip and thumb-affected finger tip pinch strengths were 95% and 90%, respectively, of the healthy side. The average pain level (as rated on a visual analog scale of 0-10) improved from a preoperative score of 9.1 to a postoperative score of 0.8. One patient was somewhat dissatisfied; all other patients were satisfied or very satisfied. All returned to their previous work at an average of 13 weeks after surgery. CONCLUSIONS: Favorable results have been achieved in this challenging scenario in the short- and middle-term in 9 of 10 patients. Previous surgery and moderate to severe wearing of the cartilage of the proximal phalanx head negatively affected the results.

Adolescent↗
PubMed2005

Reconstruction of the distal radius facet by a free vascularized osteochondral autograft: anatomic study and report of a patient.

PURPOSE: Large chondral defects of the distal radius after fractures present a reconstructive challenge. The purpose of this study was to present the anatomic findings from a cadaver of a vascularized osteochondral autograft taken from the third metatarsal appropriate for reconstructing the distal radius articular facet. A patient is presented in whom 70% of the scaphoid fossa was reconstructed with this technique. METHODS: The base of the third metatarsal was studied in the feet of 20 cadavers. The size and shape of the cartilage were measured. Additionally vessel distribution was recorded and the diameters of vascular foramina were measured with Juch's method. RESULTS: The base of the third metatarsal is pear shaped and is wider dorsally than plantarly. It averages 19.2 mm long on its main axis. Its cartilaginous surface is minimally concave or flat and it is slanted slightly proximal-dorsal to distal-plantar and proximal-peroneal to distal-tibial. Nutrient foramina were found in every case in the dorsum and on both sides of the proximal shaft. At least 1 nutrient vessel could be tracked back to the dorsalis pedis in every dissected specimen. CONCLUSIONS: The anatomic features of the base of the third metatarsal make it a potential vascularized autograft to consider for osteochondral defects of the distal radius.

Adult↗
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↗