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J A Ortega

Publications and source records attributed to J A Ortega.

At least 19 recordsLinked to original sources

Divergent selection for uterine capacity in rabbits. I. Genetic parameters and response to selection.

A 10-generation divergent selection experiment for uterine capacity (UC) measured as litter size in unilaterally ovariectomized females was carried out in rabbits. A total of 2,996 observations on uterine capacity of does (up to four parities) was recorded. Laparoscopy was performed at d 12 of their second gestation, and ovulation rate (OR) and number of implanted embryos (IE) were recorded in 735 does. Prenatal survival (PS) was assessed as UC/OR, embryo survival (ES) as IE/OR, and fetal survival (FS) as UC/IE. Genetic parameters and genetic trends were inferred using Bayesian methods. Marginal posterior distributions of all unknowns were estimated by Gibbs sampling. Heritabilities of UC, OR, IE, ES, FS, and PS were 0.11, 0.32, 0.22, 0.04, 0.14, and 0.09, respectively. Genetic and phenotypic correlations between FS and ES were low, suggesting different biological mechanisms for the two periods of survival. After 10 generations of selection, the divergence was approximately 1.5 rabbits, or approximately 1% per generation. Approximately one-half of this response was obtained in the first two generations of selection, which may suggest the presence of a major gene segregating in the base population.

Animals↗

Epidemiology of chronic inflammatory bowel disease in the Northern area of Huelva.

OBJECTIVE: To know the different epidemiologic aspects of chronic inflammatory bowel disease (IBD) in the Northern area of the province of Huelva. MATERIAL AND METHODS: we carried out a retrospective (1980-1996) and prospective (1996-2003) study of all patients diagnosed with IBD in the Northern area of Huelva, with 77,856 inhabitants. The distribution of Crohn s disease (CD) and ulcerative colitis (UC) was analyzed, as well as sex, age and smoking habit at the time of diagnosis, familial aggregation, appendicectomy rate, phenotype (anatomical site and clinical types), extraintestinal manifestations, and immunosuppressive therapy or surgical requirements. RESULTS: 70 patients with IBD were studied, 40 with UC and 30 with CD. Sex distribution was 39 (55.7%) males (55% with CD vs 56.6% with UC; NS) and 31 (44.3%) females (45% with CD vs 43.3% with UC; NS). Mean age at presentation was 44.7 +/- 19.32 years in UC vs 32.3 +/- 16.43 in CD; p < 0.001. Familial association was 7.1%. Previous appendicectomy was referred in 2.5% of patients with UC vs 36.7% of those with CD (p < 0.001), and the percentage of smokers was also higher in CD 66.7% vs CU 12.5% (p < 0.001). Anatomical site in UC was: proctitis, 20%; proctosigmoiditis/left colon, 42.5%; extensive colitis, 25%; and pancolitis, 12.5%; in CD was: terminal ileum, 43.3%; colon, 20%; and ileo-colon, 36.7%. The disease patterns were: inflammatory 56.7%, obstruction 26.7%, and fistulization 16.7%. Extraintestinal manifestations were diagnosed in 7.5% of patients with UC vs 16.6% patients with CD; surgery was performed in one patient with UC vs 10 with CD, and one patient with UC required immunosuppressive treatment vs 12 with CD. A multivariant analysis showed that younger age and smoking habit were risk factors for CD vs advanced age in UC, in which case, the smoking habit was a protective factor. The mean incidence rate of IBD starting from 1996 and expressed in cases/100,000 inhabitants/year was 5.2 for UC and 6.6 for CD. CONCLUSIONS: The mean incidence of UC in our area was 5.2 cases/100,000/inhabitants/year, and 6.6 for CD. Patients presenting with CD are diagnosed at a significantly younger age that those with UC; the smoking habit is a risk factor for CD while it protects from UC. The characteristics of IBD in our geographical area do not differ substantially from those in other regions of Spain.

Adult↗

Analyses for the presence of a major gene affecting uterine capacity in unilaterally ovariectomized rabbits.

The presence of a major gene for uterine capacity (UC), ovulation rate (OR), number of implanted embryos (IE), embryo survival (ES), fetal survival (FS), and prenatal survival (PS) was investigated in a population of rabbits divergently selected for UC for 10 generations. Selection was performed on estimated breeding values for UC up to four parities. UC was estimated as litter size in the remaining overcrowded horn of unilaterally ovariectomized does. OR and IE were counted by means of laparoscopy. Bartlett's test, Fain's test, and a complex segregation analysis using Bayesian methods were used to test for the presence of a major gene. All three tests showed that the data appeared consistent with the presence of a major gene affecting UC and IE. The results of the complex segregation analysis suggested the presence of a major gene with large effect on IE and ES (a > 1sigma(p)), at high frequency (p = 0.70 and 0.68, respectively), and with a large contribution to the total variance (R(g) = 0.39 and 0.47, respectively); and the presence of a major gene with moderate effect on each of OR, FS, PS, and UC. The results suggest that the studied reproductive traits are determined genetically by at least one gene of large effect.

Animals↗

Panhandle PCR for cDNA: a rapid method for isolation of MLL fusion transcripts involving unknown partner genes.

Identifying translocations of the MLL gene at chromosome band 11q23 is important for the characterization and treatment of leukemia. However, cytogenetic analysis does not always find the translocations and the many partner genes of MLL make molecular detection difficult. We developed cDNA panhandle PCR to identify der(11) transcripts regardless of the partner gene. By reverse transcribing first-strand cDNAs with oligonucleotides containing coding sequence from the 5' MLL breakpoint cluster region at the 5' ends and random hexamers at the 3' ends, known MLL sequence was attached to the unknown partner sequence. This enabled the formation of stem-loop templates with the fusion point of the chimeric transcript in the loop and the use of MLL primers in two-sided PCR. The assay was validated by detection of the known fusion transcript and the transcript from the normal MLL allele in the cell line MV4-11. cDNA panhandle PCR then was used to identify the fusion transcripts in two cases of treatment-related acute myeloid leukemia where the karyotypes were normal and the partner genes unknown. cDNA panhandle PCR revealed a fusion of MLL with AF-10 in one case and a fusion of MLL with ELL in the other. Alternatively spliced transcripts and exon scrambling were detectable by the method. Leukemias with normal karyotypes may contain cryptic translocations of MLL with a variety of partner genes. cDNA panhandle PCR is useful for identifying MLL translocations and determining unknown partner sequences in the fusion transcripts.

Alleles↗

Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children's Cancer Group and the Pediatric Oncology Group.

PURPOSE: Previous studies demonstrated that chemotherapy with either cisplatin, vincristine, and fluorouracil (regimen A) or cisplatin and continuous infusion doxorubicin (regimen B) improved survival in children with hepatoblastoma. The current trial is a randomized comparison of these two regimens. PATIENTS AND METHODS: Patients (N = 182) were enrolled onto study between August 1989 and December 1992. After initial surgery, patients with stage I-unfavorable histology (UH; n = 43), stage II (n = 7), stage III (n = 83), and stage IV (n = 40) hepatoblastoma were randomized to receive regimen A (n = 92) or regimen B (n = 81). Patients with stage I-favorable histology (FH; n = 9) were treated with four cycles of doxorubicin alone. RESULTS: There were no events among patients with stage I-FH disease. Five-year event-free survival (EFS) estimates were 57% (SD = 5%) and 69% (SD = 5%) for patients on regimens A and B, respectively (P =.09) with a relative risk of 1.54 (95% confidence interval, 0.93 to 2.5) for regimen A versus B. Toxicities were more frequent on regimen B. Patients with stage I-UH, stage II, stage III, or stage IV disease had 5-year EFS estimates of 91% (SD = 4%), 100%, 64% (SD = 5%), and 25% (SD = 7%), respectively. Outcome was similar for either regimen within disease stages. At postinduction surgery I, patients with stage III or IV disease who were found to be tumor-free had no events; those who had complete resections achieved a 5-year EFS of 83% (SD = 6%); other patients with stage III or IV disease had worse outcome. CONCLUSION: Treatment outcome was not significantly different between regimen A and regimen B. Excellent outcome was achieved for patients with stage I-UH and stage II hepatoblastoma and for subsets of patients with stage III disease. New treatment strategies are needed for the majority of patients with advanced-stage hepatoblastoma.

Antibiotics, Antineoplastic↗

Feasibility and toxicity of chemoembolization for children with liver tumors.

PURPOSE: To determine the feasibility, toxicity, and efficacy of hepatic arterial chemoembolization (HACE) in pediatric patients with refractory primary malignancies of the liver. PATIENTS AND METHODS: Six patients with hepatoblastoma (HB), three with hepatocellular carcinoma (HCC), and two with undifferentiated sarcoma of the liver were treated with HACE every 2 to 4 weeks until their tumors became surgically resectable or they showed signs of disease progression. All but one newly diagnosed patient with HCC had previously received systemic chemotherapy. RESULTS: All patients with HB and HCC responded to HACE, as measured by imaging studies and alpha-fetoprotein levels. Surgical resection (complete or microscopic residual disease) was feasible in five of 11 patients, and three patients remain alive with no evidence of disease. Elevated liver transaminase and bilirubin levels were seen after each one of the 46 courses of HACE. Other toxicities included fever, pain, nausea, vomiting, and transient coagulopathy. CONCLUSION: HACE is feasible, well tolerated, and effective in inducing surgical resectability of primary hepatic tumors in children.

Adolescent↗

Activity of intraarterial carboplatin as a single agent in the treatment of newly diagnosed extremity osteosarcoma.

BACKGROUND: Chemotherapy has dramatically improved the rates of cure and survival of patients with localized and metastatic osteosarcoma. Nonetheless, the number of chemotherapeutic agents active against osteosarcoma is limited to doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. Carboplatin, a cisplatin analogue, has been tested as a single agent in patients with recurrent osteosarcoma or as part of multiagent chemotherapy in newly diagnosed patients. PROCEDURE: We tested the activity and toxicity of two cycles of intraarterial carboplatin as a "window therapy" (600 mg/m2 per cycle) in 33 consecutive patients with extremity osteosarcoma before the start of multiagent chemotherapy. Response was based on clinical (tumor diameter, local inflammatory signs, and range of motion) and radiological parameters (plain local films and arteriographic studies prior to drug administration). RESULTS: Patients' age ranged between 8 and 18 years (median age 13 years). Primary tumor originated from the femur (15 patients), tibia (10 patients), fibula (4 patients), humerus (3 patients), and calcaneus (1 patient). Only 7 patients (21%) had metastatic disease at diagnosis (5 in the lung and 2 in other bones). A favorable clinical and radiological response was documented in 81% and 73% of the patients, respectively. Clinical and radiological progression occurred in 12% and 9% of the patients, respectively. Seventeen of the patients remain alive and disease-free. Survival and event-free survival at 3 years for nonmetastatic patients are 71% (SE = 9%) and 65% (SE = 9%), respectively; for metastatic patients, the figures are 17% (SE = 15%) and 14% (SE = 13%), respectively. CONCLUSIONS: We conclude that carboplatin is an active agent in the treatment of newly diagnosed extremity osteosarcoma.

Adolescent↗

Pharmacology of cytarabine given as a continuous infusion followed by mitoxantrone with and without amsacrine/etoposide as reinduction chemotherapy for relapsed or refractory pediatric acute myeloid leukemia.

BACKGROUND: The outcome of patients with acute myeloid leukemia (AML) who relapse or fail to achieve an initial remission has been dismal. PROCEDURE: Fifteen pediatric patients with AML, 4 relapsed and 11 primary refractory, were reinduced with a loading bolus of 0.5 g/m2 cytarabine (ara-C) followed immediately by a continuous infusion of ara-C (130 mg/m2/day) for 72 hours, followed with four daily doses (12 mg/m2/day) of mitoxantrone. Eight of 15 patients received an additional course of amsacrine and etoposide. RESULTS: Ten of 15 (66%) achieved complete response (CR) and 3 achieved partial response (PR) (20%), with an objective response rate of 86% after ara-C/mitoxantrone. One patient died before disease assessment, and one had no response after ara-C/mitoxantrone. Pharmacokinetic studies of ara-C and ara-U were performed in 13 of 15 patients. A steady-state (Css) ara-C concentration was achieved at 2 hours after the bolus ara-C dose and was maintained up to 72 hours. The Css plasma concentrations of ara-C and ara-U averaged 10.33 +/- 0.81 microM and 139.14 +/- 17.8 microM, respectively. Also, cellular pharmacokinetic studies of ara-CTP were performed on circulating leukemic cells from 5 patients. Four patients who had a significant increase (P = 0.0041) in their Css ara-CTP concentrations achieved CR, whereas one patient with an insignificant increase achieved PR. CONCLUSIONS: Continuous infusion of ara-C followed by mitoxantrone is an active reinduction regimen in refractory or relapsed pediatric AML patients. The addition of amsacrine and etoposide did not improve the remission induction rate. Further studies are needed in a larger patient population to confirm these observations.

Acute Disease↗

Venoocclusive disease of the liver after chemotherapy with vincristine, actinomycin D, and cyclophosphamide for the treatment of rhabdomyosarcoma. A report of the Intergroup Rhabdomyosarcoma Study Group. Childrens Cancer Group, the Pediatric Oncology Group, and the Pediatric Intergroup Statistical Center.

BACKGROUND: Venoocclusive disease (VOD) of the liver is a common complication after allogenic and autologous bone marrow transplantation for malignant disease. The authors report the unusual and unexpected complication of VOD of the liver occurring in children with rhabdomyosarcoma who were receiving vincristine, actinomycin D, and cyclophosphamide (VAC) according to the chemotherapy regimens of the Intergroup Rhabdomyosarcoma Study (IRS) IV. METHODS: The authors evaluated 821 patients with newly diagnosed rhabdomyosarcoma receiving treatment according to IRS IV who were considered at risk for VOD. RESULTS: Ten patients developed VOD of the liver for an overall incidence of 1.2%. VOD was found only after the administration of VAC chemotherapy. The highest incidence of VOD was observed among patients who had previously received vincristine and melphalan (Regimen 48). None of the patients receiving the chemotherapy regimen of vincristine and actinomycin D (Regimen 44) developed VOD. CONCLUSIONS: Patients receiving VAC-containing regimens on the IRS IV were found to be at risk for VOD. The VAC combination was used extensively in previous IRS studies (I, II, and III) and VOD was not reported during these studies, strongly suggesting that the escalation of the cyclophosphamide dose to 2.2 g/m2 (with the vincristine and actinomycin D doses and schedule remaining unchanged) triggered the development of VOD. The contributing role of previous therapy or events is unknown. At last follow-up, none of the nine surviving patients had developed recurrent VOD on continuation of chemotherapy.

Adolescent↗

Timing and magnitude of decline in alpha-fetoprotein levels in treated children with unresectable or metastatic hepatoblastoma are predictors of outcome: a report from the Children's Cancer Group.

PURPOSE: We analyzed data on 31 children with primary unresectable or metastatic hepatoblastoma (HB) to investigate possible prognostic correlations between the serum level of alpha-fetoprotein (AFP), its changes during treatment, and outcome. PATIENTS AND METHODS: Patients were treated according to the Children's Cancer Group (CCG) protocol 823F, which included an initial surgery before eight courses of chemotherapy that consisted of cisplatin immediately followed by a continuous infusion of doxorubicin. Four courses were given before and four after the second surgery. AFP levels were measured before treatment, before and after second surgery, and at the end of treatment. RESULTS: Twenty-four of 31 patients showed a decline of > or = 1 log in AFP levels before second surgery (early responders). By the end of treatment, there were 16 patients, all early responders, without clinical or radiographic evidence of tumor and with normal AFP levels. Fifteen of those 16 had a decline of > or = 2 logs in AFP before second surgery (large early response). Of the 15 patients who failed to respond to treatment, 10 died, among whom only one patient had a large early response. A large early response was the strongest independent predictor of outcome in a univariate and multivariate Cox regression model, and patients with such a response had the best survival (P < .0001). CONCLUSION: For children with unresectable or metastatic HB, early changes in AFP levels are a reliable predictor of outcome and can be used for identification of poor responders to treatment, ie, patients whose AFP level fails to decrease 2 logs before second surgery should be considered for alternative treatment.

Child↗

Comparison of buffy coat preparation to direct method for the evaluation and interpretation of bone marrow aspirates.

Bone marrow differential and French, American, British (FAB) classification of buffy coat preparation (BCP) was compared to direct method (DM) in 69 pediatric patients with various hematologic and oncologic disorders. The marrow evaluation differed significantly in 12 of 69 patients (17.4%). The differential counts were discordant in 9 out of 69 patients (13%), and the FAB classifications were discordant in 3 out of 25 patients (12%) with acute lymphoblastic leukemia (ALL). Underestimation of the percent blasts occurred with buffy coat preparation in patients with acute non-lymphoblastic leukemia (ANLL). While buffy coat preparations can facilitate morphologic evaluation in marrow malignancies, significant errors can occur in determination of the differential count. Direct smear should be used in conjunction with buffy coat smears in the evaluation of bone marrow aspirates.

Biopsy, Needle↗

Treatment of bilateral Wilms' tumor: comparison of initial biopsy and chemotherapy to initial surgical resection in the preservation of renal mass and function.

The National Wilms' Tumor Study 3 (NWTS-3) recommended treatment of bilateral Wilms' tumor with initial biopsy followed by chemotherapy with subsequent operation to resect the remaining tumor. This study was performed to determine if this approach preserves renal mass and function when compared with initial surgical resection followed by chemotherapy. Over a 20-year period (1970 to 1990), 15 patients with synchronous bilateral Wilms' tumor were treated at the Childrens Hospital of Los Angeles. Eight patients in the surgical group underwent initial unilateral nephrectomy with contralateral biopsy, wedge resection, or partial nephrectomy and subsequent chemotherapy. The seven patients in the chemotherapy group underwent bilateral tumor biopsy, followed by chemotherapy and subsequent tumor resection. Patients were assigned to each group in a nonrandomized manner according to the preference of the attending oncologist and surgeon. Comparison of the two groups showed no significant differences in sex distribution, initial renal function, tumor histology, dose and field of radiotherapy, presence or absence of positive surgical margins, and local recurrence rates. Patients in the surgery group were slightly older than those in the chemotherapy group: 3.6 +/- 2.2 versus 2.3 +/- 2.2 years. The percent of renal mass involved by tumor for the surgery group was 52 +/- 12 versus 73 +/- 16 for the chemotherapy group (P = .03). The percent of renal mass preserved following all operations, local recurrence rates, incidence of metastases, and survival was nearly identical between the two groups. There were three cases of renal failure in the surgery group and one case of renal failure in the chemotherapy group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Melanotic neuroectodermal tumor of infancy. A case report of paratesticular primary with lymph node involvement.

A 17-month-old boy had a melanotic neuroectodermal tumor of infancy in the left paratesticular region affecting the retroperitoneal lymph nodes. Immunohistochemical and ultrastructural study showed phenotypical diversity of the proliferating cells within a spectrum of neuroectodermal differentiation. Urinary catecholamine levels were initially elevated but returned to normal values after complete eradication of the tumor. The patient received chemotherapy and is now well, without evidence of disease 28 months after surgery.

Biomarkers, Tumor↗

Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group (CCSG) undertook a study (CCG-823F) to test the feasibility of administering continuous infusion doxorubicin (CI DOX) and cisplatin (CDDP) in patients with unresectable or incompletely resected hepatoblastoma (HB) or hepatocellular carcinoma (HCC). Chemotherapy consisted of CI DOX 20 mg/m2/d for days 1 to 4 and CDDP 100 mg/m2 on day 1 followed by a 21-day rest period. Second-look surgery was performed after the administration of four chemotherapy courses. Forty-seven (47) assessable patients were entered on study, 33 with HB and 14 with HCC; of these, 34 (26 HB and eight HCC) completed the initial four courses of chemotherapy. Of the 26 HB patients, 25 were evaluated as responding to chemotherapy before the scheduled second-look procedure and were considered surgically resectable at that time. Surgery was performed on 22 patients; three patients refused the second-look surgery. Nine patients had no evidence of residual malignant disease, seven underwent surgical resection of remaining tumor, four were left with microscopic residual disease, one had a partial resection with gross tumor left behind, and one remained unresectable. Nine HCC patients completed four chemotherapy courses. Eight patients achieved a partial remission and second-look surgery was attempted on seven. Only two had all malignant disease removed at the second procedure. Data from 225 courses of chemotherapy were evaluated for toxicity. Neutropenia (absolute granulocyte count less than 500/mL) was observed in 68 courses, and five of these episodes were associated with sepsis. Severe mucositis was documented in 21 courses, and hypomagnesemia (magnesium less than 1.2 mg) was noted in 30 patients. Two patients developed decreased left ventricular shortening fraction, which resolved when chemotherapy was discontinued. In summary, CI DOX plus CDDP is a well-tolerated and effective regimen in inducing surgical resectability in HB patients who are unresectable at diagnosis and significantly improves survival for this group of patients to 66.6%.

Adolescent↗

Clinical features and results of therapy for children with paraspinal soft tissue sarcoma: a report of the Intergroup Rhabdomyosarcoma Study.

Soft tissue sarcomas of the paraspinal region comprised 3.3% (56 of 1,688) of the patients entered and eligible on Intergroup Rhabdomyosarcoma Studies I (IRS-I) and II (IRS-II) (1972 to 1984). These lesions tended to be greater than 5 cm in diameter at diagnosis, invaded the spinal extradural space, and were of the extraosseous Ewing's sarcoma or undifferentiated sarcoma subtype in 55% (30 of 56) of the cases. Patients with tumors in clinical groups II, III, and IV were treated with radiotherapy (XRT) and vincristine-dactinomycin (VA) or VA plus cyclophosphamide (VAC) +/- doxorubicin. Clinical group I patients treated on IRS-II did not receive XRT, while those on IRS-I were randomized to receive VAC +/- XRT. Forty-four of the paraspinal patients (79%) achieved a complete response (CR) compared with 77% (1,260 of 1,632) for patients with disease in other sites. Twenty-seven patients (55%) subsequently relapsed (five local, three regional, four local and distant, and 14 distant). The proportion of patients surviving 5 years by clinical group (stage) from I to IV were 50%, 50%, 62%, and 27%, respectively. Paraspinal patients had somewhat poorer survival than patients with disease in other sites, both in IRS-I and IRS-II; the percentage of paraspinal patients surviving 5 years was 50% and 52% for IRS-I and IRS-II, respectively, whereas these percentages were 55% and 63% for patients with disease in other sites. Histology did not influence the CR rate, but unexpectedly, patients who had embryonal rhabdomyosarcoma (RMS) had the poorest overall survival rate. We concluded that patients with paraspinal lesions may require extended-field radiation therapy to reduce the high local failure rate and more intensive chemotherapy to achieve better local and systemic tumor control.

Child↗

Role of chemotherapy in pediatric pulmonary blastoma.

Pulmonary blastoma is a rare malignant tumor of the lung that has been treated primarily with surgery. The effect of combination chemotherapy has not been systematically investigated. Two pediatric cases are reported in whom combination chemotherapy consisting of vincristine, actinomycin-D, cyclophosphamide, cis-platinum, and adriamycin was successfully used. The first case, a 5-year-old boy, underwent incomplete surgical excision of the tumor followed by a 104-week course of combination chemotherapy. The second case is a 3-year-old boy who was initially treated with combination chemotherapy that resulted in an objective response; he subsequently underwent surgical excision. This intensive combination chemotherapy is effective both in inoperable tumors as initial therapy as well as a surgical adjuvant.

Antineoplastic Combined Chemotherapy Protocols↗