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J Cortes

Publications and source records attributed to J Cortes.

At least 91 records · Page 5Linked to original sources
PubMed1998

Determinants of prognosis in late chronic-phase chronic myelogenous leukemia.

PURPOSE: Since interferon alfa (IFN-A) became an established treatment in chronic myelogenous leukemia (CML), more patients are referred to tertiary centers in late chronic phase (ie, > 12 months after diagnosis). Trials conducted in this phase cannot be evaluated precisely unless the features that determine prognosis in late chronic-phase CML are identified. The purpose of this study is to define the prognostic determinants of late chronic-phase CML. PATIENTS AND METHODS: From 1980 to 1997,257 consecutive CML patients referred in late chronic phase were studied. Their clinical characteristics at the time of referral and their association with survival were investigated. A staging model was designed. RESULTS: The median survival from time of referral was 43 months. Pretreatment characteristics associated with worse outcome included older age, poor performance status, splenomegaly, low albumin level, high percentage of blasts or basophils in peripheral blood (PB) or bone marrow, longer duration of chronic phase, and poor-risk group as defined by the Synthesis model. Prior exposure to IFN-A was not associated with worse outcome. By multivariate analysis, characteristics associated with shorter survival were age of 60 years or older, time from diagnosis of 3 years or greater, performance status of 1 or greater, PB basophils of 7% or greater, spleen 10 cm or greater, PB blasts 3% or greater, and albumin level less than 4 g/dL. A model that included age, duration of chronic phase, performance status, and PB basophils was generated. Patients with no, one, two, or three or greater adverse factors had median survivals of 71, 49, 26, and 19 months, respectively. CONCLUSION: A staging model for late chronic-phase CML can stratify patients in four groups with significantly different outcomes. If confirmed in independent populations, such a model could be considered in the analysis of future trials of treatment strategies in late chronic-phase CML.

Adolescent↗
PubMed1997

Influence of weight and gonadal status on total and regional bone mineral content and on weight-bearing and non-weight-bearing bones, measured by dual-energy X-ray absosorptiometry.

OBJECTIVE: To evaluate the influence of weight on total body bone mineral content (BMCTB) and regional body bone mineral content (head, arms, trunk and legs). This was studied in accordance with gonadal status and the weight-bearing or non-weight-bearing status of each region. METHODS: The study included 94 postmenopausal women (mean age 60.6 +/- 10.5 years), 36 perimenopausal women (mean age 49.0 +/- 2.3 years) and 60 premenopausal women (mean age 36.1 +/- 6.9 years). Full-body bone densitometry (DXA), for measuring total body bone and regional bone mineral content, was carried out in all the women. RESULTS: Among these groups, the influence of 1 kg of body weight on total and regional bone mineral content (percent) did not differ (paired test P ns). In the overall group of women, paired comparison showed differences between the head and other zones measured (P = 0.036-0.004). In the overall group of women, no differences were found in the percent influence of 1 kg body weight on bone mineral content in any study zone (by ANOVA, Fisher's PLSD post hoc test and the Kruskal-Wallis test). In the overall group of women, Fisher's r to z test revealed a non-significant relationship between weight and the bone mineral content of the head (r = 0.49, P ns) but in every other region the relationship between weight and bone mineral content was significant (r = 0.36-0.54, P < 0.0001 in all). CONCLUSIONS: The effect of body weight on BMCTB and regional did not differ significantly with either gonadal status or weight-bearing (legs) and non-weight-bearing bones (arms).

Absorptiometry, Photon↗
PubMed1997

Natural history and staging of chronic myelogenous leukaemia.

The natural history of chronic myelogenous leukaemia has changed in recent years, partly as a result of earlier diagnosis but mostly as a consequence of the availability of effective therapies that have the potential to eradicate the Philadelphia-positive clone. The prognostic models designed in the pre-interferon-alpha (IFN-alpha) era based on clinical characteristics of the disease are still useful in identifying different risk groups after treatment with IFN-alpha, but achieving a cytogenetic response with IFN-alpha is now the most important prognostic factor for survival. The significance of other molecular and biological variables remains to be determined.

Antineoplastic Agents↗
PubMed1997

Treatment of chronic myelogenous leukemia with nucleoside analogs deoxycoformycin and fludarabine.

In vitro studies suggest that nucleoside analogs have an antileukemic effect against chronic myelogenous leukemia (CML). We investigated the antileukemia effect of deoxycoformycin (DCF) and fludarabine in patients with CML. Four patients with Philadelphia chromosome (Ph)-positive CML were treated with DCF at 4 mg/m2 every week for 4 weeks, then every other week for four doses, and then every month as maintenance. Two patients were in late chronic phase and two in accelerated phase. All had previously failed therapy with interferon-alpha (IFN-A). Nine patients were treated with fludarabine 30 mg/m2/day for 5 days every 28 days. Three had Ph-positive CML, and six Ph-negative disease. Five patients were in accelerated phase and four in late chronic phase. Three patients treated with DCF had normalization of WBC counts while on the weekly schedule but progressed when changed to every other week. The fourth patient had no objective response. There were no cytogenetic responses. DCF was well tolerated with only mild nausea and vomiting in all patients. Patients treated with fludarabine received a median of two courses (range 1-4). In two patients (both Ph-positive), disease progressed to blastic phase upon recovery. Two other patients died of hemorrhagic complications secondary to thrombocytopenia. In all other cases fludarabine produced a transient reduction of WBC counts, but counts recovered to levels equal to or greater than the pre-treatment values. There were no cytogenetic responses. These results, together with previous experience with 2-CDA producing only hematologic responses, suggest that nucleoside analogs may not have a significant role in the management of CML.

Adult↗
PubMed1997

A pilot study of all-trans retinoic acid in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

Retinoids have significant antiproliferative effect against chronic myelogenous leukemia (CML) cells in vitro. We conducted a pilot study to investigate the clinical effect of all-trans retinoic acid (ATRA) in patients with CML. Thirteen patients with Philadelphia chromosome (Ph)-positive CML in late chronic phase (n=7), accelerated phase (n=5), or blastic phase (n=1) were treated. All had been previously treated and 12 (92%) had disease refractory to interferon-alpha therapy. They received ATRA 175 mg/m2 orally in two divided doses daily until disease progression. The median duration of therapy was 56 days (range 11 to 190). Only one patient in late chronic phase had a transient decrease in WBC counts; all other patients in late chronic phase showed no response to therapy. Four of the five patients in accelerated phase showed evidence of antileukemia effect manifested by a decrease in bone marrow and/or peripheral blood blasts, promyelocyte and/or basophil percentages. In all cases the response was transient. The patient in blastic phase had no evidence of antileukemic effect. The treatment was well tolerated with the major side-effects being headache, nausea, dry skin, and dry mucosal membranes. One patient required dose reductions due to toxicity. We conclude that in this population of patients with extensively treated, advanced stage, Ph-positive CML, ATRA alone is ineffective for long-term therapy. The antileukemia effect seen in some patients warrants further investigation of retinoids in other schedules and in combinations in patients with CML.

Adolescent↗
PubMed1997

Analysis of the BCR-ABL protein in Philadelphia chromosome-positive adult acute lymphocytic leukemia.

Philadelphia chromosome (Ph)-positive acute lymphocytic leukemia (ALL) constitutes 15-35% of all ALL in adults. Its detection is prognostically significant. The Ph abnormality is usually detected through standard cytogenetic analysis but 20-30% of patients have insufficient metaphases (IM) with such analysis. To detect the BCR-ABL oncoprotein in peripheral blood specimen of patients with ALL at the time of diagnosis and at follow-up, a new sensitive technique of enhanced chemiluminescence Western blot (ECL-WB) analysis was investigated. Among 41 patients with newly diagnosed ALL, nine were Ph positive by cytogenetic studies; they were also BCR-ABL positive according to ECL-WB. Eight had p190 disease, and one had p210 disease. Among the 16 patients with IM, none demonstrated the oncoprotein through ECL-WB or through simultaneous Southern blot (SB) for p210 rearrangement. Follow-up studies were available for seven patients: four had detectable protein and three of them relapsed 4-20 weeks later; three had undetectable protein and one of them (who had low level protein at the time of diagnosis) relapsed 11 weeks later. Although none of the patients with IM at diagnosis had detectable protein according to ECL-WB, this was probably due to the small number of patients studied. One patient with IM studied at follow-up demonstrated the protein by ECL-WB. In summary, we describe a technique that is useful in the detection of p190/p210 ALL at diagnosis. It is less time consuming, and more cost effective than standard chromosome banding techniques. It may also detect the oncoprotein in cases with IM. Although a larger number of patients should be studied to prove its clinical usefulness, this technique may also be of value for monitoring residual disease at follow-up.

Blotting, Western↗
PubMed1997

Interleukin-10 in non-Hodgkin's lymphoma.

Interleukin-10 (IL-10) is a pleiotropic cytokine produced by type 2 helper cells (Th2), as well as by monocytes and macrophages, and normal and neoplastic B lymphocytes. It is highly homologous to an open reading frame of Epstein-Barr virus (EBV) called BCRF1, and EBV infection of B-cells up-regulates IL-10. IL-10 production has strong immunosuppressive effects via inhibition of Th1 type cytokines, including interferon gamma and interleukin-2. On B-cells, IL-10 has a potent stimulating effect, inducing proliferation and differentiation. Interestingly, in cell lines derived from B-cell lymphomas, IL-10 production has been found to be up-regulated, and it serves as an autocrine growth factor. In patients with non-Hodgkin's lymphoma (NHL), serum IL-10 levels are significantly increased when compared to normal individuals and NHL patients in remission. The prognostic significance of these increased levels vary according to the assay used. Both human IL-10 and viral IL-10 are increased, and when specific assays for human IL-10 are used, there seems to be no prognostic significance, whereas when the assay cross-reacts with viral IL-10, high levels correlate with poor prognosis. These results suggest that viral IL-10 might have some pathogenic role in NHL.

Animals↗
PubMed1996

The development of blood transfusion: the contributions of Norman Bethune in the Spanish Civil War (1936-1939).

Although the Spanish Civil War (1936-1939) has been the focus of many papers in many countries, there are few references concerning medicine during this war, and many of the related events and medical progress are not well known. Some of these events came to influence civilian and military medicine. Among these were advances in blood transfusion, in which the Canadian surgeon, Norman Bethune, played an important role, particularly in advocating transfusion of blood to soldiers at the front rather than at medical centres behind the lines. While much of Bethune's work, especially in Canada and China, is well known, 1-3 certain aspects of Bethune's work and his stay in Spain are worth reviewing.

Blood Transfusion↗
PubMed1996

Result of interferon-alpha therapy in patients with chronic myelogenous leukemia 60 years of age and older.

PURPOSE: To determine the response rate to interferon-alpha (IFN-alpha) in patients with chronic myelogenous leukemia (CML) aged 60 years and older. PATIENTS AND METHODS: Patients with CML aged 60 years and older included in all protocols with INF-alpha therapy for chronic phase CML at the M.D. Anderson Cancer Center were analyzed. They were treated with human leukocyte or recombinant human IFN-alpha 5x10(6) U/m2 daily alone or in combination with hydroxyurea or IFN gamma. The clinical characteristics of the patients were analyzed and their hematologic and cytogenetic responses to IFN-alpha and survival from the initiation of therapy were determined. Results were compared with those of younger patients treated in the same protocols. Treatment-related toxicity was also analyzed. RESULTS: Thirty-five of 274 (13%) patients included in trials of IFN-alpha-based regimens for CML were 60 years and older. Older patients had a higher percentage of bone marrow blasts (P = 0.04) and basophils (P = 0.09) than younger patients. Sixty-nine percent achieved a complete hematologic remission with IFN-alpha therapy, and 51% had a cytogenetic response, which was major in 26% and complete (Philadelphia chromosome-positive cells = 0%) in 20%, Their median survival was 64 months, and the estimated 5-year survival rate was 62%. These results were not different from those in younger patients. Twenty-two patients (63%) had at least grade 2 toxicity requiring dose adjustment. The most frequent side effects were neurotoxicity in 31% and chronic fatigue in 29%. CONCLUSIONS: Patients with CML 60 years of age and older respond well to IFN-alpha therapy, but experience more toxicity. This therapy should be considered for these patients if they are otherwise in good condition, with careful attention to IFN-alpha toxicity and its management.

Age Factors↗
PubMed1996

Disseminated intravascular coagulation in adult acute lymphoblastic leukemia: frequent complications with fibrinogen levels less than 100 mg/dl.

In order to establish the frequency and clinical complications of DIC during remission induction of untreated adults with acute lymphoblastic leukemia, we retrospectively reviewed the records of 125 consecutive patients treated with vincristine, doxorubicin, and dexamethasone but without L-asparaginase. DIC, defined as hypofibrinogenemia in the presence of elevated fibrin-fibrinogen degradation products, was detected at presentation in 10% of 99 and during remission induction in 67% of 58 patients who were screened for DIC. Elevated levels of D-dimers (DD) were seen in all eight patients with DIC in whom they were measured. All cases of DIC were diagnosed by the ninth day of induction and were associated with infection in 15 of 39 patients. DIC did not cause any deaths but was temporally associated with two thromboses and four hemorrhages in six of the 16 patients with fibrinogen levels < 100 mg/dl but with only one hemorrhage among 23 patients (4%) with fibrinogen levels > 100 mg/dl (P < 0.01). Heparin was not administered to any patient, whereas platelets were administered to all to maintain platelet counts > 20 x 10(9)/l. Fresh frozen plasma (FFP) and/or cryoprecipitate were administered 26 patients resulting in a contemporaneous correction of the coagulopathy and in control of hemorrhages and thromboses. We conclude that DIC is rare at presentation but common during induction of adult ALL and is frequently associated with clinical complications when fibrinogen levels are < 100 mg/dl. We recommend daily testing of fibrinogen, PT, and DD during the first 10 days of induction, and for the patients with DIC platelet transfusions to maintain counts > 20 x 10(9)/l, and when fibrinogen levels fall below 100 mg/dl transfusions of FFP and/or cryoprecipitate. Additional studies are needed to determine the optimal management of the DIC during remission induction of adult acute lymphoblastic leukemia.

Adult↗
PubMed1995

The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia.

Although central nervous system (CNS) leukemic relapse is frequent in adult acute lymphocytic leukemia (ALL), the need for prophylaxis in different risk groups for CNS relapse, the value of high-dose systemic and intrathecal (IT) chemotherapy, and the timing of prophylaxis are not well defined. This analysis was conducted to investigate these questions and to assess the value of a risk-oriented CNS prophylaxis approach. We analyzed the incidence of CNS leukemia after initiation of therapy in patients treated on 4 consecutive trials for adult ALL including different CNS prophylactic modalities. The treatment groups included (1) the program preceeding the vincristine-Adriamycin-dexamethasone (VAD) regimen, with no CNS prophylaxis; (2) the VAD regimen with prophylaxis using high-dose systemic chemotherapy; (3) the modified VAD program with high-dose systemic chemotherapy to all patients and IT chemotherapy for high-risk patients after achieving complete remission; and (4) the hyperCVAD program with early high-dose systemic and IT chemotherapy starting during induction to all patients, with more IT injections (16IT) administered to the high-risk group for CNS relapse compared with the low-risk group (4IT). A total of 391 patients were included, 73 of whom were treated with preVAD, 112 with VAD, 114 with modified VAD, and 92 with hyperCVAD. The overall CNS relapse rates were 31%, 18%, 17%, and 3%, respectively for the 4 groups (P < .001). For the high-risk group for CNS relapse, they were 42%, 26%, 20%, and 2%, respectively (P < .001). The differences in CNS relapse rates in the low-risk group were not statistically significant. At 3 years, the overall CNS leukemia event-free rates were 48%, 76%, and 98%, respectively (P < .001). In the high-risk group, the CNS event-free rates were 38%, 66%, 75%, and 98%, respectively (P < .001); however, there was no difference in the low-risk group. We conclude that (1) high-dose systemic chemotherapy is a useful prophylactic measure; (2) early IT chemotherapy is necessary to reduce the incidence of CNS leukemia overall and in the high-risk group; and (3) a risk-oriented approach is appropriate to tailor the intensity of CNS prophylaxis.

Adolescent↗
PubMed1995

Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage.

Macrocyclic polyketides exhibit an impressive range of medically useful activities, and there is great interest in manipulating the genes that govern their synthesis. The 6-deoxyerythronolide B synthase (DEBS) of Saccharopolyspora erythraea, which synthesizes the aglycone core of the antibiotic erythromycin A, has been modified by repositioning of a chain-terminating cyclase domain to the carboxyl-terminus of DEBS1, the multienzyme that catalyzes the first two rounds of polyketide chain extension. The resulting mutant markedly accelerates formation of the predicted triketide lactone, compared to a control in which the repositioned domain is inactive. Repositioning of the cyclase should be generally useful for redirecting polyketide synthesis to obtain polyketides of specified chain lengths.

Base Sequence↗
PubMed1995

[Anatomic bone and dento-alveolar changes in patients with lip incompetence].

Twenty young patients with clinical labial incompetence have been studied cefalometrically using Delaire's Analysis, in order to determine anatomical alterations who explains this condition. In all of them we have found some anatomical alteration in sagital or vertical plane or both, in maxillary or mandibular squeletal bases or their dento-alveolar squeletic unit. Knowledge of anatomical factors contributing or determining labial incompetence is the key of the planification and execution of an etiologic approach, what is the best way to obtain physiological rapport and consequently good aesthetic results.

Adolescent↗
PubMed1995

Correlation of specific platelet activation markers with carotid arterial wall thickness.

Many studies have shown increased platelet activation in patients with coronary artery, cerebrovascular and peripheral vascular diseases. However, the temporal relationship between platelet activation and arterial atherosclerosis is unclear. To answer this basic question, we measured the plasma concentrations of two specific platelet activation markers, beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) in 459 cases with increased carotid arterial wall thickness and 459 age-, sex-and race-matched controls selected from a cohort of 15,800 men and women, aged 45-64 who participated in the Atherosclerosis Risk in Communities Study. These participants had no acute vascular symptoms or known cardiovascular disease. The mean values of beta TG and PF4 were significantly higher in cases than in controls. However, when analyzed by quartiles using conditional logistic regression, only beta TG exhibited a significant association with carotid wall thickness, while PF4 did not. The odds ratio (OR) determined by multivariate logistic regression analysis was significantly higher for the uppermost quartile of beta TG (OR=1.7, 95% CI 1.1-2.5) compared to the lower 3 quartiles. This OR was 2.3 in white men (95% CI 1.2-4.2), 1.4 in white women (95% CI 0.6-3.0) and 1.0 in blacks (95% CI 0.4-2.5). This study indicates that plasma beta TG may be useful as a marker for early atherosclerosis in middle aged adults, particularly in white men. It also suggests that platelet activation has an independent role in the pathogenesis of atherosclerosis, although the possibility that this may be a response to carotid atherosclerosis cannot be excluded.

Biomarkers↗
PubMed1994

Abnormalities in the long arm of chromosome 11 (11q) in patients with de novo and secondary acute myelogenous leukemias and myelodysplastic syndromes.

Leukemias with abnormalities in chromosome 11q23 occur frequently after exposure to topoisomerase II-reactive drugs. We investigated the characteristics and outcome of patients with de novo or secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) with abnormalities in chromosome 11q. Sixty-one patients had 11q abnormalities. Alterations involved 11q23 in 38 patients and other 11q abnormalities in 23. Sixteen patients had secondary disease, 12 involving 11q23, and four with other 11q abnormalities; 26 patients with de novo disease had 11q23 abnormalities and 19 other 11q abnormalities. The most common 11q23 abnormality was t(9;11), significantly more common in secondary (9/12) than in de novo (6/26) leukemias (p = 0.003). There were no significant differences in clinical characteristics between de novo and secondary groups involving 11q23. Five of 12 patients (42%) with secondary and 20/26 (77%) with de novo disease achieved complete remission (p = 0.05). Median survival was 6 weeks in the secondary group and 71 weeks in the de novo group (p = 0.001). There were no long-term survivors in either group. Results are similar when other 11q abnormalities are included. Adults with AML or MDS with 11q abnormalities secondary to prior chemotherapy have a worse prognosis than patients presenting de novo. However, 11q abnormalities define a population with a poor prognosis even when presenting de novo.

Adolescent↗
PubMed1994

[Vertical condylar hyperplasia, clinical and histologic aspects. Apropos of 2 cases].

Condylar hyperplasia is a pathologic condition associated with an overgrowing of the condylar cartilage. It is possible to distinguish two clinical forms; vertical and horizontal when the lesion is unilateral. We have reported two cases of vertical condylar hyperplasia, both of them treated by simple condylectomy, in our opinion the selected treatment. Histopathological images show an increase of the growth and maturation layers of the condylar cartilage and inclusions of cartilaginous tissue, with appearance of glove fingers into the underlying cancellous bone.

Adult↗
PubMed1994

Antibiotic prophylaxis in Wertheim-Meigs surgery. A single dose vs three doses.

A prospective, randomized study to compare the prophylactic efficacy of a single dose of piperacillin with that of a three doses, was carried out with patients undergoing Wertheim-Meigs surgery. The results demonstrate that in this case three doses of piperacillin have a higher efficacy than one dose in the prevention of febrile complications and post-operative infections.

Abscess↗