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Biomedical subjects

M A Rodriguez

Publications and source records attributed to M A Rodriguez.

At least 109 records · Page 6Linked to original sources
PubMed1994

High incidence of monosomy 18 in lymphoid malignancies that have bone marrow and peripheral blood involvement.

We studied the incidence of numerical chromosome 18 abnormalities in 107 patients with lymphoid malignancies by fluorescence in situ hybridization (FISH) using a directly conjugated centromeric probe for chromosome 18. Samples were obtained by fine needle aspiration of diseased nodes, bone marrows or peripheral blood. Monosomy 18 was more common in chronic lymphocytic leukemia (43%), small lymphocytic lymphoma (28%), and follicular lymphomas (12.5%) than in diffuse lymphomas (5.3%; p < 0.01). Monosomy 18 was detected in 9.7-17.1% of the cells in non-Hodgkin's lymphoma (NHL) (background, 5.4%; 99% CI, 4.2%-6.6%) and in 8%-16.7% (median, 10%) of the cells in (CLL) (background, 3.4%; 99% CI, 2.5%-4.3%). All patients with monosomy 18 were found to have bone marrow involvement. Of all untreated patients who had disease involving the bone marrow, 32% were found to have monosomy 18. Trisomy 18 was detected in 3.6%-48.2% of the cells in NHL (background, 0.9%; 99% CI, 0.2%-1.6%) and was most common in diffuse large-cell lymphoma (34%) and follicular lymphomas (31%). None of the patients with small lymphocytic lymphoma or chronic lymphocytic leukemia had trisomy 18. There was no correlation between trisomy 18 and response to treatment or clinical presentation. In this study, monosomy 18 was observed frequently in patients with lymphoid malignancies that involve the bone marrow and peripheral blood. Our data suggest that important gene(s) located on chromosome 18 may be involved in homing of the malignant lymphocytes to the bone marrow and peripheral blood.

Adult↗
PubMed1994

Stage, serum LDH, and performance status predict disease progression and survival in HIV-associated lymphomas.

PURPOSE: This is a review of treatment of 44 patients with positive HIV serology (positive HIV) and lymphoma. MATERIALS AND METHODS: Twenty patients had diffuse large-cell lymphoma (DLCL), and 18 had small noncleaved-cell lymphoma (SNCCL). Three had Hodgkin's disease (HD) and 3 had diffuse small- or mixed-cell lymphoma. These patients received intensive chemotherapy regimens for management of their disease; most were regimens in use at our institution for patients with lymphoma who did not have positive HIV. RESULTS: The complete response to treatment (CR) was 77% for all patient, 80% for those with DLCL, and 72% for those with SNCCL. Stage, serum LDH, and performance status were predictors of complete remission and freedom from progression. Though there was a tendency for patients with a T4-cell count of < or = 200 to have a higher risk of opportunistic infections while receiving therapy, most infections were controllable with appropriate antibiotic management. More than one-half of the deaths in this study occurred after completion of therapy in complete remission, with a median survival of only 11 months, and were attributable to AIDS-related complications. CONCLUSIONS: Our data suggest that (1) patients with lymphoma who have positive HIV have responses to chemotherapy similar to those expected for patients who are HIV-negative; (2) most infectious complications are manageable with appropriate therapy during treatment; and (3) after completion of chemotherapy, treatment should focus on control of progression of AIDS-related complications.

AIDS-Related Opportunistic Infections↗
PubMed1994

The gallium scan predicts relapse in patients with Hodgkin's disease treated with combined modality therapy.

The gallium scan (GS) is an important indicator of disease activity in untreated Hodgkin's disease, especially in the upper torso, and may be an important predictor of results for patients who have completed chemotherapy and radiotherapy (XRT). To better define the importance of the GS in predicting treatment results in a group of patients treated with uniform therapy, we performed GS prior to treatment in 46 patients with pathologically or clinically staged I-III Hodgkin's disease who received three cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) followed by XRT. Staging methods included computerized tomography (CT) of the chest, abdomen, and pelvis, lymphangiogram, and the GS, using 8 to 10 millicuries with single photon emission computed tomography (SPECT) of the upper and lower torso. Only 3 patients had negative GS before chemotherapy. After three cycles of NOVP and prior to XRT, the other 43 had repeat GS performed. Complete remission (CR) was judged by disappearance of disease after all therapy without considering GS results. The CR for those with initial positive GS was 93%. The three-year freedom from progression result for stage I-II was 94%, and the three-year overall survival was 96%; corresponding results for stage III were 86% and 100%, respectively. None of the prognostic factors for analysis, including bulky adenopathy, hilar involvement, or B symptoms, was an important predictor of results. However, only 1 of the 33 with a negative GS after these NOVP has had progressive disease compared to 3 of the 10 with a GS that remained positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Intensive conventional-dose chemotherapy for stage IV low-grade lymphoma: high remission rates and reversion to negative of peripheral blood bcl-2 rearrangement.

BACKGROUND: Advanced-stage low-grade lymphoma is characterized by initial responsiveness to many conventional therapies but ultimate relapse. Intensive therapy approaches with non-cross-resistant regimens have not been extensively explored. The polymerase chain reaction (PCR) can be used to monitor for the presence of cells with rearrangement of bcl-2, and provides a sensitive and stringent parameter of disease activity and treatment response that may have clinical utility. PATIENTS AND METHODS: From 1988 to 1992, 138 evaluable patients were treated with 3 sequential chemotherapy regimens, as well as with interferon alfa 2b (IFN) in combination with corticosteroids. Nineteen patients had serial PCR monitoring for bcl-2 rearrangement. RESULTS: Among a subset of 58 patients who had an initial phase of IFN plus prednisone, the response rate was 59%, mostly partial remissions (PR). With the chemotherapy program, 65% have achieved complete remission to date, and 30% PR. By PCR analysis, 13 of 19 tested achieved negative status ('molecular remission'), a much higher frequency of molecular remission than has been seen with standard therapies, and these molecular remissions appear to correlate with a lower likelihood of relapse. CONCLUSIONS: Intensive conventional-dose chemotherapy can achieve high rates of remission, even when monitored by the stringent PCR technique.

Adult↗
PubMed1994

Primary mediastinal large cell lymphoma is characterized by an inverted pattern of large tumoral mass and low beta 2 microglobulin levels in serum and frequently elevated levels of serum lactate dehydrogenase.

BACKGROUND: Primary mediastinal large cell lymphoma (PMLCL) is an emerging entity. New parameters can help define it. MATERIALS AND METHODS: Retrospective analysis of medical records from 35 patients treated at The University of Texas M.D. Anderson Cancer Center from 1985 to 1990. Immunohistochemical evaluation of tissue specimens. Determination of survival (S) and time to treatment failure (TTF). RESULTS: The median age was 34 years and 69% were females. Eight-three percent presented with symptoms of mediastinal involvement. While 100% of the patients presented with bulky mediastinal disease and 72% had elevated pretreatment serum lactate dehydrogenase, only 6% presented with an elevated pretreatment serum beta 2 microglobulin. The lymphoma cells lacked CD21 staining. For the 18 patients treated initially at M.D. Anderson Cancer Center, S and TTF curves rates after doxorubicin-based regimens (plus radiotherapy in 14 cases) were 72% and 61%, respectively, at 5 years follow-up (median, 42 months). Four out of six patients who received autologous bone marrow transplant as salvage therapy are currently alive without disease at follow-up times of 21, 25, 32, and 54 months. CONCLUSION: Primary mediastinal large cell lymphoma has characteristic clinicopathological features to which another can be added, that of an inverted pattern of bulky disease, high LDH and low beta 2 M in serum. The response to therapy is comparable to that of intermediate-grade lymphomas, although the numbers in the study are small. Our preliminary data suggest a possible role for autologous bone marrow transplantation (ABMT) as salvage therapy.

Adult↗
PubMed1994

Temperature-metabolism relations in the cotton-top tamarin (Saguinus oedipus) model for ulcerative colitis.

Examination of temperature-metabolism relations found no significant differences between thermoregulation of temperature housed laboratory cotton-top tamarins (Saguinus oedipus) and wild tamarins in Colombia, S.A. The results indicate that tamarins do not acclimate to a temperature environment and are metabolically stressed at Ta less than 32 degrees C. This is consistent with an hypothesis of chronic metabolic stress as a factor in the etiology of cotton-top tamarin colitis, which is restricted to captive populations and not found in wild tamarins.

Acclimatization↗
PubMed1994

Phase I study of the combination of fludarabine, mitoxantrone, and dexamethasone in low-grade lymphoma.

PURPOSE: Fludarabine is an active agent for patients with low-grade lymphoma (LGL) but has mainly been used as a single agent. This trial was designed to define the maximum-tolerated dose (MTD) of a combination of fludarabine, mitoxantrone, and dexamethasone (FND), to identify the toxicities of these agents in combination, and to make preliminary observations about the efficacy of this combination. PATIENTS AND METHODS: Twenty-one patients with recurrent LGL or follicular large-cell lymphoma were treated, in cohorts of three, at stepwise escalating doses. Patients were required to have adequate marrow function and normal renal, hepatic, and cardiac function. RESULTS: The MTD of the combination was found to be as follows: fludarabine, 25 mg/m2/d (days 1 to 3); mitoxantrone, 10 mg/m2 (day 1); and dexamethasone, 20 mg/d (days 1 to 5). Each course was administered monthly, and up to eight courses were given. Dose-limiting toxicities were neutropenia and infections. Thrombocytopenia was modest. Nonhematologic toxicity was very modest. Responses were seen at every dose level. The overall response rate was 71%, with a 43% complete remission (CR) rate. The median duration of CR was 18 months (with follow-up duration from 13 to 28+ months). CONCLUSION: FND was well tolerated in this population. While our primary aim was to define the MTD, our preliminary observations on the efficacy of the regimen were favorable. The overall response rate was high, there was a high fraction of CRs, and our early impression is that these responses are durable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study.

PURPOSE: This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients. PATIENTS AND METHODS: The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied. RESULTS: Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL. CONCLUSION: ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.

Adolescent↗
PubMed1994

[Effect of the in vivo administration of beta-methyldigoxin on the Na, K-ATPase measured in different tissues of guinea pigs].

We measured the activity of the Na,K ATPase, Mg dependent and inhibited by ouabain, in microsomal fractions obtained from guinea pig myocardium and kidney, as weel as red cell ghosts. A group of animal was treated with beta-methyl digoxin (0.2 mg intraperitoneally) about one hour before obtaining the tissues. The control group received no medication. The plasma of both group, control and treated, had similar potassium concentrations (4.3 +/- 0.87 mM and 4.3 +/- 0.66 mM, respectively). The plasma digoxin concentrations from treated animals was always high (76.4 +/- 34.1 ng/ml). The Na,K-ATPase activity in the microsomal fraction from treated animals decreased by 28.7% in myocardium and by 27.7% in red cell ghosts, in comparison to the enzime activity measured in control animals. On the other hand, the Na/K activity obtained in kidney microsomal fraction did not change with treatment. We then measured the Na,K-ATPase activity in the red cell ghosts and microsomal fractions obtained from myocardium and kidney of untreated Guinea pigs. Adding digoxin in vitro (1 x 10(-9) M to 1 x 10(-3) M) we obtained, in myocardial fractions, a 50% maximal inhibition; the digoxin concentration causing half maximal effect (DI50) was 7 x 10(-5) M. In the kidney microsomal fraction we measured a 66% maximal inhibition of the enzime activity and DI50 was 2 x 10(-6) M. For red cell ghosts the maximal enzime inhibition was 34% and the DI50 was 1 x 10(-5) M. In conclusion, in the Guinea pig, the acute in vivo administration of beta-methyl digoxin causes a parallel inhibition of the Na,K-ATPase from myocardial fractions and red cell ghosts. We measured no significant change in the kidney microsomal fractions. We propose the determination of red cell Na,K-ATPase activity as possible indicator of digitalis effect on humans treated with these drugs.

Animals↗
PubMed1993

Hodgkin's disease: study of treatment intensities and incidences of second malignancies.

BACKGROUND: Advances in radiotherapy and chemotherapy have gradually increased cure rates for patients with Hodgkin's disease. With improved long-term survivals, increases in observed second malignancies over those of the general population have been reported as early as 1972. Recently, a number of investigators have suggested that the relative importance of recognized risk factors contributing to the development of acute myelogenous leukemia (AML), non-Hodgkin's lymphomas, and solid tumors may be different. Our study is concerned with the influence of various risk factors on patients who have been treated with modern radiotherapy and combination chemotherapy between 1966 and 1987. PATIENTS AND METHODS: We reviewed the records of 1,022 patients with Hodgkin's disease of whom 1,013 had sufficient data for analysis. Kaplan-Meier methodology was used to calculate overall and determinate survivals and occurrences of acute myelogenous leukemia, non-Hodgkin's lymphoma, and solid tumors. The observed to expected incidences, calculated from the SEER incidence and population files for 1976, were compared. Using Cox's proportional hazards model, the following were analyzed singly for risk significance for the entire population: age, stage, splenectomy, treatment modality, treatment intensity, and number of treated relapses. Separate analyses were performed to determine the relative risks for subsets of the population. These included pelvic radiotherapy for those with stage III disease and specific alkylating agents for patients who were treated with chemotherapy only. RESULTS: Sixty-six instances of second malignancy were documented as follows: AML 14, non-Hodgkin's lymphoma 14, and solid tumors 38. The overall incidence of second malignancy was significantly greater than the expected incidence of 21.75 (p = 0.0001) and it was also significant for AML, non-Hodgkin's lymphoma and solid tumors. Analyses for risk of second malignancy demonstrated that age > or = 40 years, stage III or stage IV disease, and treatment with chemotherapy only were all associated with a significantly higher risk of second malignancy than any of the other factors. However, only treatment with regimens containing nitrogen mustard had a significantly higher risk for second malignancy. Treatment intensity and number of treated relapses had no specific effect on risk. Joint modeling of age, stage, and treatment showed that the combination of age and stage was the most significant risk factor for AML and non-Hodgkin's lymphoma (p = < 0.0003). However, only age was important for solid tumors. CONCLUSIONS: Our analysis suggests that the most critical host factor for developing a second malignancy was age. The fact that patients with stages III and IV disease had an increased risk of second malignancy regardless of age suggests that biologic factors related to the tumor also may have been significant. However, it is possible that the effect of treatment was hidden by stage.

Actuarial Analysis↗
PubMed1993

CHOP-Bleo plus interferon for stage IV low-grade lymphoma.

BACKGROUND: Alpha interferon (IFN) is an effective single agent for patients with low-grade lymphoma, but until 1982 had not been integrated with standard chemotherapy for these patients. Since relapse from complete remission (CR) is the rule for patients with advanced stage low-grade lymphoma, a maintenance IFN schedule was explored for patients in CR. PATIENTS AND METHODS: From 1982-1987, 127 patients with stage IV low-grade lymphoma were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) for 9-18 mo. (median 13 mo.), followed by interferon alfa-n-1 (Wellferon) maintenance therapy for 24 mo. for CRs. RESULTS: The overall response rate for the entire treatment program was 73% CR and 23% partial remission. The median follow up was 59 months. At 5 years, survival was 74%, failure-free survival (FFS) 47%, and FFS of CRs 60%. Compared to a group of 96 patients with similar pretreatment clinical features treated with CHOP-Bleo from 1972-1982, this represents a significant improvement for both overall FFS (p = 0.01) and FFS of CRs (P < 0.01). Toxicity from the IFN maintenance was generally acceptable, but even at the modest dose employed in this trial (3 x 10(6) U/m2 three times weekly), dose modification was required in more than 30% of patients, usually because of fatigue. CONCLUSIONS: The integration of IFN and conventional chemotherapy is feasible and effective. Maintenance IFN prolongs remission duration for patients with stage IV low-grade lymphoma.

Adult↗
PubMed1993

Increased proportion of responders to a murine anti-CD3 monoclonal antibody of the IgG1 class in patients with systemic lupus erythematosus (SLE).

A group of Venezuelan patients with SLE showed an increased proportion of responders to Leu-4, an anti-CD3 MoAb of the IgG1 class, compared with ethnically matched non-SLE patients and healthy controls. The rate of proliferative responses or IL-2 production induced by MoAb Leu-4, and the helper effect of macrophages from Leu-4 responders on T cells from a third-party donor were comparable in patients and controls. No significant differences in the binding of murine IgG1 molecules by macrophages from SLE patients and controls were observed. The proportion of monocytes/macrophages expressing Fc gamma RI was significantly higher in SLE patients. However, the expression of FcRII, the type capable of supporting Leu-4-mediated responses, and of Fc gamma RIII was comparable in monocytes from SLE patients and controls. Our results suggest that Venezuelan patients with SLE may have a genetic predisposition for the expression of the phenotypic variant of Fc gamma RII capable of binding murine IgG1 molecules.

Adolescent↗
PubMed1992

Reversible ATP-dependent inactivation of adipose diacylglycerol acyltransferase.

Diacylglycerol acyltransferase from rat adipose tissue is shown to be inactivated by 30 to 40% upon incubation with adenosine 5'-triphosphate (ATP) and Mg2+. The activity responsible for this inactivation is associated with the cytosolic fraction, specific for ATP, prevented when ATP is substituted by beta,gamma-methylene-ATP, and partially blocked by 1 mM ethylenediaminetetraacetate or 40 mM NaF, but not by inhibitors of adenosine 3',5'-cyclic-monophosphate (cAMP)-dependent protein kinase and/or protein kinase C (PKC). The cytosolic activity cannot be mimicked by (cAMP)-protein kinase nor by PKC. Inactivated diacylglycerol acyltransferase from ATP/cytosol-treated microsomes can be reactivated by incubation with partially purified protein phosphate from rat liver, and can be inactivated again by further addition of ATP in the presence of cytosol. The results suggest the existence in adipose tissue of a protein kinase other than cAMP-protein kinase or PKC, which may be involved in the regulation of triacylglycerol synthesis.

Acyltransferases↗
PubMed1992

Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin's disease.

Between 1956 and 1990, 775 women were treated for Hodgkin's disease at The University of Texas M.D. Anderson Cancer Center. Of these, 25 (3.2%) were pregnant at diagnosis. Seven of these women were in the first trimester, 10 in the second, and eight in the third. Prior to treatment, three women in the third trimester had normal deliveries, and six patients in the first trimester had abortions. Sixteen patients received radiotherapy for supradiaphragmatic presentations during their pregnancies. All these patients had nodular sclerosing Hodgkin's disease: Two had clinical stage IA presentations and 14 had clinical stage IIA. In two patients radiotherapy (35 Gy) was limited to the neck, three patients were treated definitively to the neck and mediastinum (40 Gy), and 11 patients received mantle irradiation (40 Gy). Four to five half-value layers of lead were used to shield the uterus during radiotherapy. The dose to the fetus was estimated individually in nine patients, using a combination of an Alderson-Rando and a water phantom. The estimated total dose to the mid-fetus ranged from 1.4 to 5.5 cGy for treatment with 6 MV photons, and from 10 to 13.6 cGy for Cobalt 60. All 16 patients subsequently delivered full-term, normal infants. Following delivery, all of the patients had further staging procedures; eight received additional treatment. Subsequently, the disease relapsed in four patients; two eventually died of Hodgkin's disease. The 10-year determinant and overall survival rates were 83% and 71%, respectively. Currently, all offspring are physically and mentally normal, and none has developed a malignancy. Radiotherapy is an appropriate initial treatment for supradiaphragmatic presentations of Hodgkin's disease during the second and third trimesters of pregnancy, provided special attention is paid to treatment and shielding techniques. The outcome for women treated with irradiation for clinical stage I and II Hodgkin's disease during pregnancy has not been shown to be adversely affected by pregnancy, and after the first 8 weeks of gestation, the risk to the fetus appears to be minimal.

Female↗
PubMed1992

Isolation of inclusion bodies from vegetative Clostridium perfringens: partial purification of a 47 kDa inclusion protein.

A refractile inclusion body produced by vegetative cells of Clostridium perfringens at temperatures above 40 degrees C was isolated and partially characterized. The inclusion was composed of protein and could be solubilized by sodium dodecyl sulphate plus either dithiothreitol or beta-mercaptoethanol. The solubilized inclusion showed no antigenic relationship with Cl. perfringens enterotoxin. One major band with an apparent MW of 47 kDa was demonstrated after polyacrylamide gel electrophoresis of the solubilized inclusion. Both enterotoxin-positive and enterotoxin-negative strains produced the inclusion body. No effect on the morphology of several eucaryotic cell lines was observed when solubilized or intact inclusion was added to the cell cultures.

Animals↗