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O Tugal

Publications and source records attributed to O Tugal.

At least 19 recordsLinked to original sources
PubMed2003

Telomere dynamics in childhood leukemia and solid tumors: a follow-up study.

Telomeres of hematopoietic cells shorten with age, possibly contributing to the aging-associated hematopoietic pathology (immunosenescence, malignant transformation). Accelerated telomere shortening is seen with replicative stress, such as during administration of serial chemotherapy cycles for the treatment of childhood cancer. To define the long-term consequences of pediatric cancer treatment on hematopoietic cell telomere length, we undertook a prospective 4-year follow-up study of a 61-patient cohort of pediatric malignancies in a community-based setting. We found that mononuclear cells (MNC) and granulocytes of children with standard-risk acute lymphoblastic leukemia (ALL) suffered minimal telomere shortening throughout therapy (less than 1 kbp; average follow-up, 20 months), while those of children with solid tumors showed greater and more heterogenous telomere attrition (0.5-2.8 kbp, average follow-up, 9 months). In addition, we evaluated the role of telomerase, the enzyme commonly up-regulated in pediatric leukemic and solid tumor cells for telomere length maintenance, as a disease marker. Serial determinations of telomerase in MNC were useful to confirm disease remission in leukemia, but play no role in the follow-up of children with solid tumors.

Adolescent↗
PubMed2001

Hyperdiploidy in a case of favorable histology Wilms tumor.

Hyperdiploidy is useful in defining histologic variants of Wilms tumor and prognosis in other childhood cancers. We describe a case of hyperdiploid favorable histology Wilms tumor (50,XY,+6,+7,+8,+10,+12,-21[2]/51,idem,+9[6]/46,XY[12]) in a 3-year-old boy, and review the literature for other hyperdiploid childhood renal lesions.

Child, Preschool↗
PubMed2000

Cytogenetic abnormalities during clinical, immunophenotypic, and molecular remission in pediatric acute lymphoblastic leukemia.

The significance of random cytogenetic abnormalities detected in pediatric acute lymphoblastic leukemia (ALL) during remission is unknown. We studied 10 of 72 consecutive ALL patients who developed cytogenetic abnormalities during clinical remission to determine their effect on remission status. The cytogenetic abnormalities occurred at a median of 14.5 months (range 5-72) from the initial diagnosis. Five abnormalities were designated as clonal (monosomy 21 in three metaphases and 64 approximately 69,XXY in three metaphases from one patient at different times, and del(20)(q12q13) in three metaphases, add(13)(q34) in two metaphases, and ?del(19)(p11) in two metaphases from three different patients). Seven abnormalities were previously described: del(5)(q12), del(5)(q33), -7, del(11)(q23), +12, and +13 each in one metaphase, and del(20)(q12q13) in three metaphases). The remaining cytogenetic abnormalities were nonclonal and random. Flow cytometry and analysis of IgH and TcR gene rearrangements showed that all evaluable patients were in immunophenotypic and molecular remission, respectively. Eight patients remain in clinical and molecular remission a median of 9 months (range 7-18) after detecting the cytogenetic abnormality, and the leukemia in two patients has relapsed. During remission, cytogenetic abnormalities may not be a harbinger of leukemia relapse in pediatric ALL; therefore, a wait-and-see approach is prudent.

Aneuploidy↗
PubMed1999

Quantitation of leukemia clone-specific antigen gene rearrangements by a single-step PCR and fluorescence-based detection method.

PCR-based detection of minimal residual disease (MRD) in children with precursor B cell acute lymphoblastic leukemia (pre-B ALL) by amplification of clone-specific antigen gene rearrangements has been labor-intensive. In this study we present a simpler, yet accurate, method to assess and quantitate MRD in pediatric pre-B ALL that utilizes these markers. From the sequence of the immunoglobulin heavy chain (IgH) and T cell receptor (TcR) gene rearrangements characterized at the time of diagnosis or relapse, primers were designed and tested in a clone-specific, single-round PCR assay, then analyzed by fluorescence staining of the PCR products. The most critical step involved an adherence to a new set of guidelines for the design of clone-specific primers. Application of this method to 54 IgH and 13 TcR (nine Vdelta2Ddelta3 and four Ddelta2-Ddelta3) gene rearrangements in 47 patients resulted in an intense band within the region of the predicted molecular weight, confirming the reproducibility of the assay. Quantitative applications of the approach were examined by performing a 10-replicate limiting dilution clone-specific PCR on six diagnostic samples and an asymptotic response model of the Von Krogh form was found to fit the data well. From this model, estimation of leukemic cells of remission bone marrow samples was achieved at a detection sensitivity of 2 x 10(-6). The method is demonstrated on 18 patients whose marrows were prospectively analyzed during therapy. We conclude this methodology is useful in the quick and accurate assessment of MRD in children with pre-B ALL, and could be applied to other DNA quantitation assays.

Antigens, Neoplasm↗
PubMed1999

Randomized double-blind comparison of single high-dose ondansetron and multiple standard-dose ondansetron in chemotherapy-naive pediatric oncology patients.

This prospective, double-blind, randomized study compares the antiemetic efficacy of an equivalent dose of ondansetron administered as a single high dose or as multiple standard doses in pediatric oncology patients. Thirty-one chemotherapy-naive patients were randomized at diagnosis to receive either single high-dose ondansetron (0.6 mg/kg, maximum dose 32 mg) or multiple standard-dose ondansetron (0.15 mg/kg, maximum dose 8 mg, every 4 hr for four doses). Antiemetic efficacy was assessed by an emesis scale described as follows: 1, no nausea or emesis; 2, nauseous but able to eat; 3, nauseous and unable to eat; and 4, emesis. Sixteen patients received high-dose and 15 received standard-dose ondansetron. Patients receiving moderately or severely emetogenic chemotherapy were evenly distributed between the two treatment groups. Eighty-one percent of patients receiving high-dose and 80% receiving standard-dose ondansetron rated 1 or 2 on the emesis scale (p = 0.93). No patient experienced any clinical or laboratory toxicity. Our study suggests that single high-dose ondansetron is as efficacious as the multiple standard-dose regimen and is well tolerated. Its use will facilitate the administration of ondansetron in pediatric patients receiving chemotherapy.

Adolescent↗
PubMed1998

Isochromosome 7q and Wilms tumor.

Isochromosome 7q is a nonrandom cytogenetic abnormality in Wilms tumor. Two notable cases are described: (1) a case of bilateral Wilms tumor in which only the left-sided tumor contained isochromosome 7q and (2) a case of left-sided Wilms tumor in which the tumor contained isochromosome 7q, in addition to four other chromosomal abnormalities associated with Wilms tumor.

Child, Preschool↗
PubMed1998

Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy.

Telomerase activity and telomere length in mononuclear cells (MNCs) and granulocytes from peripheral blood (PB) and bone marrow (BM) specimens were studied in pediatric acute leukemia (ALL, n = 15; AML, n = 11) and pediatric solid tumor (ST) patients (n = 9) at diagnosis, during and after chemotherapy. In four ST patients, tumor tissue was also available. For comparative analysis, MNCs from healthy donors (n = 53) were analyzed. Telomerase was evaluated using a modified telomeric repeat amplification protocol (TRAP) assay, and telomere length by terminal restriction fragment (TRF) analysis. At diagnosis, high telomerase activity was detected in MNCs from all leukemia patients, which was similar to the activity from ST biopsy specimens. This exceeded by 10- to 20-fold the activity in PB MNCs from ST patients and healthy donors (P < 0.05). Granulocyte fractions lacked telomerase activity in all groups. BM MNCs in leukemia patients revealed a four-fold higher telomerase activity than PB (P = 0.005). After induction chemotherapy and response to treatment, telomerase activity decreased to borderline or undetectable levels in PB MNCs in leukemia (P < 0.01). Average telomeres in PB MNCs from pediatric patients were significantly longer (n = 25; 10.9 kbp) than telomeres in PB and BM MNCs from adult healthy donors (7.45 kbp) (P < 0.0001). At diagnosis, telomeres were shorter from BM compared to PB specimens in leukemia (P < 0.05), and two peak TRFs were observed corresponding to the malignant and normal cell clones. With the attainment of remission, the lower TRF peak, reflecting the leukemic population, was lost. In leukemia patients, mean TRFs increased on average 2.2 kbp after induction chemotherapy, but decreased thereafter on consolidation and maintenance chemotherapy (1 kbp). This was comparable to an average telomere loss of 1.2 kbp in PB specimens from ST patients after chemotherapy. In all patients, telomere loss in granulocytes as compared to MNCs was more pronounced with 1.8 vs 1 kbp, respectively (P = 0.014). Our results demonstrate that at diagnosis, telomerase was consistently and highly upregulated in BM and PB specimens in leukemia, decreased after induction therapy, and correlated with remission. BM specimens in leukemia had higher telomerase activity, probably due to the greater leukemic burden than in PB. Telomeres were significantly longer in children than in adults, but shortened as a consequence of chemotherapy with repeated cycles of hematopoietic regeneration. In acute leukemia, with the loss of the leukemic burden after induction chemotherapy, longer mean TRFs were found, a reflection of the repopulation with normal cells. Our findings suggest that telomerase activity may be useful in the management of childhood malignancies. The significance of telomere length shortening in pediatric patients undergoing chemotherapy and possible telomere regeneration after myelosuppressive treatment remain to be determined.

Adolescent↗
PubMed1997

Prenatally diagnosed neuroblastoma.

BACKGROUND: Prenatally diagnosed neuroblastomas have been reported in increasing numbers over the past several years, and there are now a few reviews based on up to 21 cases. The purpose of this article is to review the clinical and biologic features of prenatally diagnosed neuroblastoma based on a review of 55 cases. METHODS: A review was conducted of 3 cases seen at the study institution and 52 other cases reported thus far in the literature. RESULTS: Prenatal diagnosis was made usually after 32 weeks of gestation. Approximately 93% of the tumors were adrenal in origin, and 44% of these were cystic. Thirty-seven patients (67%) had Stage I disease, 12 (22%) had Stage IV-S disease, and only 3 (5%) had Stage IV disease. The DNA index was favorable (> 1) in 14 of 16 patients studied. None of these 16 patients studied had amplification of the N-myc oncogene. Catecholamines were elevated in only 33% of the patients. The liver was the most common site of dissemination, which was observed in 25% of patients; bone involvement was not observed in any patient. Ultrasonography failed to detect existing hepatic metastasis in three patients. Primary surgical resection was performed in 47 patients (85%). Chemotherapy was given to five patients and radiotherapy to three. Of the 50 patients for whom follow-up information was available, 45 (90%) were alive at a range of 2-120 months from diagnosis. CONCLUSIONS: Prenatally diagnosed neuroblastomas are predominantly adrenal in origin and frequently cystic. The liver is the most common site of dissemination and bone involvement is notably absent. The vast majority of these infants have a favorable stage of disease (I, II, and IV-S) and favorable biologic features, and consequently have an excellent prognosis. Although surgery alone is curative for most patients, a period of observation may avoid surgery in some individuals who may achieve spontaneous regression.

Adrenal Gland Neoplasms↗
PubMed1996

Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia.

PURPOSE: This open-label pilot study was designed (1) to determine the effect of hydroxyurea on the hemoglobin level in children with sickle cell anemia, (2) to evaluate the toxicity of hydroxyurea, and (3) to assess any impact of hydroxyurea on the frequency of vaso-occlusive crises (VOCs). PATIENTS AND METHODS: Ten children (group 1) with three or more VOCs of the extremities or two or more VOCs of the lungs (acute chest syndrome) in the preceding 12 months, and five children (group 2) with hemoglobin levels less than 70 gm/L were treated with hydroxyurea in doses of 20 to 35 mg/kg per day. The frequency of VOCs before hydroxyurea therapy was compared with the frequency during therapy, and the peak hemoglobin levels during hydroxyurea therapy were compared with the pretreatment values. RESULTS: One patient in group 1 was removed from the study within 1 month because of nausea. Seven of the remaining nine patients in group 1 had a decrease in the frequency of VOCs. The number of VOCs per patient-year for all 14 patients decreased from 2.5 before hydroxyurea therapy to 0.87 during hydroxyurea therapy, a decrease of 65% (p < 0.00001). Two of five patients in group 2 had an increase in hemoglobin of 27 gm/L and 34 gm/L over the baseline. The median rise in hemoglobin was 19 gm/L (range, 7 to 37) for all 14 patients. Nine patients are still receiving hydroxyurea for a median period of 23 months (range, 18 to 59). CONCLUSIONS: Hydroxyurea decreases the severity of anemia in some patients, and it may decrease the frequency of VOC. Its short-term hematologic toxicity is minimal.

Adolescent↗
PubMed1996

Gastric ganglioneuroblastoma: a rare finding in an infant with multifocal ganglioneuroblastoma.

PURPOSE: This report describes a female infant with stage 4 multifocal ganglioneuroblastoma with gastric involvement. PATIENT: The patient had a right cervical tumor, a left posterior mediastinal tumor, bilateral adrenal tumors, and bony and bone marrow metastases. The tumor cells were diploid and lacked N-myc gene amplification. The gastric involvement, which did not produce clinical symptoms, was only detected by meticulous exploration during laparotomy. RESULTS: Our patient achieved only a partial response to alternating cycles of cyclophosphamide, vincristine, and adriamycin; and etoposide and cisplatin. She currently has stable, unresectable disease with elevated catecholamines. CONCLUSIONS: Multifocal ganglioneuroblastomas may arise from either neuroblastic rests or aberrant deposits of neuroblasts. The latter mechanism may have accounted for our patient's gastric tumor. Patients with multifocal ganglioneuroblastomas warrant meticulous radiographic and surgical evaluation to completely document the full extent of disease, and to ensure appropriate staging and therapy.

Female↗
PubMed1994

Recurrent benign intracranial hypertension due to iron deficiency anemia. Case report and review of the literature.

PURPOSE: Iron deficiency anemia (IDA) causes benign intracranial hypertension (BIH). PATIENTS AND METHODS: A case of an 11-year-old girl with severe IDA and benign intracranial hypertension is presented. RESULTS: Treatment of iron deficiency resulted in the resolution of BIH. Recurrence of BIH is observed with the recurrence of IDA. Chronic intermittent blood loss from the intestinal polyps was the etiology of recurrent IDA. CONCLUSIONS: A thorough search to determine the etiology of IDA is essential for proper treatment. Although BIH is a rare complication of IDA, its association with IDA should be recognized for prompt treatment before an extensive and costly workup for BIH is done.

Adolescent↗
PubMed1994

Recombinant human granulocyte colony stimulating factor in cyclic neutropenia: use of a new 3-day-a-week regimen.

BACKGROUND: G-CSF has been shown to be beneficial in cyclic neutropenia when given as a daily subcutaneous injection. We investigated the usefulness of a new three-day-a-week regimen. METHODS: A ten year old boy with cyclic neutropenia was initially treated with G-CSF 7 micrograms/kg given on alternate days for seven months. He was then placed on the same dose, given three days a week. The effectiveness of these regimens were assessed by serial CBCs and by the frequency and duration of the symptoms. RESULTS: The mean absolute neutrophil count (ANC) increased from 1282 before therapy to 11,718/microliters on alternate day regimen and 7716/microliters on three-day-a-week regimen. The nadir ANC improved from 30/microliters before therapy to 546/microliters and 198/microliters on treatment. The duration and frequency of mouth sores were significantly less on therapy, and there was an estimated cost savings of $23,826/year on three-day-a-week regimen compared to a daily regimen. CONCLUSION: The three-day-a-week G-CSF regimen is clinically effective and cost saving in the treatment of cyclic neutropenia and should be studied in a larger cohort of patients.

Child↗
PubMed1994

Transient erythroblastopenia of the newborn caused by human parvovirus.

PURPOSE: We describe a newborn baby boy with anemia in whom human parvovirus (HPV) antibodies were detected in his serum. PATIENTS AND METHODS: Severe reticulocytopenia and anemia lasted until day 11 after his birth. Thereafter reticulocytosis was observed. Work-ups for immune hemolytic anemia, fetomaternal hemorrhage, placental hemorrhage, intrauterine infections were negative by clinical and laboratory analysis. HPV-specific IgM and IgG were positive on both the baby's and the maternal serum. RESULTS: Despite severe anemia, the baby remained clinically stable. His hemoglobin levels steadily increased along with ongoing reticulocytosis. He is now 14 months old with normal hemoglobin. CONCLUSIONS: Detection of HPV antibodies indicated its causal relation to the development of congenital pure red cell aplasia. The possibility of HPV infection should be considered in the assessment of anemia of the newborn.

Antibodies, Viral↗
PubMed1993

Transfusion therapy for severe anemia.

PURPOSE: We evaluated the safety and efficacy of a new transfusion regimen for children with severe anemia. PATIENTS AND METHODS: Twenty-two consecutive patients with severe anemia (hemoglobin < 5 g/dl) of gradual onset requiring transfusion of packed red blood cells (PRBC) were studied. The transfusion regimen consisted of continuous infusion of PRBC at the rate of 2 cc/kg/h until the desired volume was given. Throughout the transfusion, the patients were closely monitored for any clinical signs of heart failure. The rise in hematocrit per 1 cc of PRBC/kg transfused was computed for each patient. RESULTS: No patient developed any signs of cardiac failure or increase in the heart rate during or after the completion of transfusion. All patients had a decrease in the heart rate by the completion of transfusion. The mean decrease in the heart rate was 28% of the pretransfusion heart rate (range 12-44%). Excluding the four patients with sickle cell anemia, the remaining 18 patients had a mean increase in the hematocrit of 1.04% per 1 cc/kg of PRBC (range 0.85-1.28). CONCLUSION: We conclude that for children with severe anemia of gradual onset requiring transfusion therapy, continuous transfusion of PRBC at the rate of 2 cc/kg/h is a safe and effective regimen resulting in an increase in the hematocrit of approximately 1% for each 1 cc/kg of PRBC transfused in all patients, except patients with sickle cell anemia.

Acute Disease↗
PubMed1992

Home chemotherapy for children with cancer.

A program was established in which the parents of children with cancer were trained to administer intravenous chemotherapy to the children in their homes. The main objectives of this program (Home Intravenous Chemotherapy by Parents [HICP]) were to improve the quality of life for children with cancer and their parents and to decrease the cost of medical care for these children by decreasing the number of clinic visits and hospital stays intended solely for the administration of chemotherapy. Twenty-four months of experience with this program indicates that with a close communication network and a good working relationship among a home care organization (HCO), the parents of the patient, a pediatric oncology nurse, and an attending pediatric oncologist, many chemotherapeutic agents can be safely administered to these children by their parents in their homes. The patients and their parents are enthusiastic about this program because of the valuable time saved and the increased participation in care. In addition, this program greatly decreased the cost of medical care for these children.

Adolescent↗
PubMed1989

Combined occurrence of chyloperitoneum and chylothorax after surgery and chemotherapy for Wilms' tumor.

Chyloperitoneum is an extremely rare complication of abdominal surgery in children and a combined occurrence of chylothorax and chyloperitoneum after abdominal surgery has never been reported in children. Chylous ascites usually occurs as a result of operative trauma to the thoracic duct, cisterna chyli, or its tributaries. About one third of all patients with chylous ascites after retroperitoneal lymph node dissection also develop secondary chylothorax. Diaphragmatic defects have been shown to be responsible for the occurrence of chylothorax secondary to chyloperitoneum. Congenital diaphragmatic weakness may result in evagination of the peritoneum causing diaphragmatic blebs, the rupture of which results in the movement of the peritoneal fluid into the pleural cavity. In the authors' patient, the rent in the diaphragm that occurred during surgery was probably responsible for the chylothorax. The role of chemotherapy, if any, in the pathophysiology of this complication is unknown. Total parenteral nutrition (TPN) is a simple and effective treatment for postoperative chylous effusions. Surgical treatments such as abdominal exploration for the repair of leaking lymphatics and peritoneovenous shunt should be reserved for patients who fail TPN.

Chylothorax↗