Search PubMed⌕ Search

Biomedical subjects

W A Smithson

Publications and source records attributed to W A Smithson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Phase II trial of indicine N-oxide in relapsed pediatric solid tumors. A report from the Childrens Cancer Study Group.

We used indicine N-oxide to treat 46 children with malignant solid tumors: 17 with osteosarcoma, 12 with neuroblastoma, 13 with a brain tumor, and 4 with other miscellaneous tumors. The efficacy and toxicity of the drug was assessed at the dose of 2000 mg/m2/day for five consecutive days. None of the 39 patients evaluable for response achieved a complete or partial response. Hepatotoxicity was experienced by 13 patients: 11 patients developed asymptomatic elevations of transaminases, 1 patient developed hyperbilirubinemia, and 1 developed ascites. Indicine N-oxide appears to be ineffective in the treatment of osteosarcoma, neuroblastoma, and pediatric brain tumors at this dose and schedule. Because higher doses are associated with an unacceptably high incidence of severe, irreversible hepatotoxicity, we do not recommend further study of this agent in pediatric solid tumors.

Adolescent↗
PubMed1990

The role of timing of high-dose cytosine arabinoside intensification and of maintenance therapy in the treatment of children with acute nonlymphocytic leukemia.

The Children's Cancer Study Group instituted a pilot study to investigate the use of high doses of cytosine arabinoside (AraC) in the intensification phase of treatment for acute nonlymphocytic leukemia (ANLL). Patients achieving remission and not eligible for allogeneic bone marrow transplantation were treated with four doses of high-dose AraC and L-asparaginase. These drugs were repeated either on or after 28 days (q28 days), after recovery of hematologic parameters (for the first 49 patients entered onto this trial); or after 7 days (q7 days), despite dropping blood counts (for the last 53 patients enrolled). After completing an additional 3 months of intensification therapy, patients were then allocated by physician choice to either discontinue therapy or receive 18 28-day cycles of maintenance therapy, including the daily administration of 6-thioguanine. Despite three deaths associated with the toxicity of the aggressive (q7 days) AraC timing, patients receiving this approach demonstrated equal or better disease-free survival from the end of induction (55% versus 42% actuarially at 3 years [P = 0.52]). Maintenance therapy appeared to play no role in improving outcome for people who received the aggressive timing of AraC cycles. Fifty-nine percent were alive disease free actuarially at 3 years from the decision to not give maintenance therapy (n = 27) compared with 62% for those receiving maintenance therapy (n = 16; P = 0.49). On the other hand, patients who received the less aggressive AraC intensification timing (q28 days) had an improved survival rate if maintenance therapy was administered (n = 17) (65% versus 39% for patients not receiving maintenance therapy [n = 24] at 3 years [P = 0.07]). Maintenance therapy therefore may not improve outcome in patients receiving aggressive timing of high-dose AraC but may be important in less intensive postremission regimens in childhood ANLL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Pediatric urological complications with intraoperative radiation therapy.

Intraoperative radiotherapy with variable energy electrons has been used as a supplemental boost to treat 6 children with locally advanced retroperitoneal malignancies. Of the patients 4 had treatment-related injuries to portions of the urinary tract within the intraoperative and external radiation fields. Three patients had significant renal impairment requiring surgical correction. The pathogenesis and management of treatment-induced injury to the urinary tract are discussed.

Adolescent↗
PubMed1990

Pediatric reference intervals for 19 biologic variables in healthy children.

We defined age- and sex-specific reference intervals for 19 biologic variables in serum samples from healthy children, 1 to 22 years of age, using common laboratory equipment. Upper and lower reference intervals were defined as the estimated 2.5 and 97.5 percentiles of the distribution. For variables (y) that varied with age, the relationship of y to age was modeled with polynomial regression. Parametric percentile estimates specific to each age were then calculated as the predicted y value +/- 1.96 . SD, in which SD = the standard deviation of the residuals. For variables not associated with age, the nonparametric 2.5 and 97.5 sample percentiles were used to define the reference intervals. No significant age or sex differences were found for serum sodium, total protein, glucose, direct bilirubin, or albumin. Potassium, chloride, and urea showed constant values in children that were higher than adult values in the case of potassium and chloride and lower than adult values in the case of urea. No sex-related differences were seen for these analytes. Creatinine, uric acid, and bicarbonate showed an upward trend in values with increasing age, whereas aspartate aminotransferase, phosphorus, and total and ionized calcium showed a downward trend with increasing age. Sex-related differences were noted for these analytes. The immunoglobulins (IgG, IgA, and IgM) showed an upward trend with increasing age, with no sex-related differences except for IgM in children.

Adolescent↗
PubMed1989

Extraosseous Ewing's sarcoma. A study of 42 cases.

Fifty patients at the Mayo Clinic (Rochester, MN) from 1935 to 1985 met the histologic criteria for extraosseous Ewing's sarcoma. Forty-two had soft tissue primaries without bony involvement and formed the basis for this retrospective study of the clinical behavior and management of extraosseous Ewing's sarcoma. There were 19 male and 23 female patients (mean age, 22 years). Metastases were documented in 30 of the patients, six at the time of presentation and 24 occurring up to 11 years later, most commonly to lungs or bone. Three patients were lost to follow-up. Sixteen of 35 patients (46%) had local recurrence. Overall survival was 15 of 39 (38.5%) at 5 years. Decreased survival was noted with pelvic tumors, incomplete resections, and presence of metastatic disease, whereas increased survival was associated with wide surgical resection with negative microscopic margins, adjuvant local radiation therapy, and presentation since 1970 (48% 5-year survival compared with 28% before 1970).

Adolescent↗
PubMed1989

Clinical outcome in children with acute cerebellar encephalopathy and neuroblastoma.

Acute cerebellar encephalopathy (ACE)--ataxia often associated with opsoclonus, polymyoclonus, and irritability--may be associated with neuroblastoma and should be suspected in a child who presents with ACE. The survival in ten children with ACE associated with neuroblastoma was 100%. Most of the tumors were ganglioneuroblastomas. The abdomen was the most common location for the tumor in this study although it also can be found in the mediastinum. All patients with this syndrome had a localized tumor. With ACTH therapy, ACE may resolve early postoperatively, but it tends to recur in most patients, continuing for as long as 3 years after the initial operation. Treatment with ACTH or prednisone modifies and rapidly clears the symptoms during the acute episode of recurrent ACE as well as helps to resolve subsequent neurologic sequelae. Significant neurologic sequelae persisted in seven of ten patients and included deficits in cognition or intellect, hyperactivity, impulsivity, emotional lability, and mild motor deficits. Seizures were seen in one patient.

Abdominal Neoplasms↗
PubMed1989

Acute megakaryocytic leukemia (M7) in children.

We analyzed the clinical and laboratory features of eight children (median age, 20 months; range, 13 months to 11 years) with acute megakaryocytic leukemia (M7) and compared the findings with those reported in the literature. The diagnosis was supported by ultrastructural examination for platelet peroxidase or immunophenotyping for glycoprotein IIb/IIIa or the von Willebrand factor protein. Two patients had Down's syndrome. Initial findings included anemia (in all patients), thrombocytopenia (in six), myelofibrosis (in three), lytic bone lesions (in two), and pronounced leukocytosis (in one). Stem cell culture studies of peripheral blood specimens revealed an aberrant phenotype of the megakaryocytes in one patient and reversal to a normal pattern after successful therapy. Remission was achieved in seven of the eight patients after aggressive chemotherapy, and four patients remained in remission 27 to 57 months after diagnosis. Three of these four patients underwent allogeneic bone marrow transplantation. M7 leukemia is not infrequent in children younger than 3 years of age, especially in those with Down's syndrome. The availability of monoclonal antibodies specific to restricted antigens of the megakaryocytic lineage has made the diagnosis of M7 leukemia both possible and practical.

Anemia↗
PubMed1989

Immunocytochemical study of small round cell tumors in routinely processed specimens.

Fourteen commercially available monoclonal antibodies were used to examine, by the indirect immunoperoxidase technique, 20 formaldehyde solution-fixed, routinely processed bone marrow biopsy and surgical biopsy specimens from a group of small round cell tumors with bone marrow involvement, including 6 neuroblastomas, 4 rhabdomyosarcomas, 3 Ewing's sarcomas, 3 Burkitt's lymphomas, and 4 small-cell carcinomas of the lung. Eight of 14 monoclonal antibodies worked well on the routinely processed sections. Antidesmin (D33) (Dako Corp, Santa Barbara, Calif) and anti-muscle actin (HHF35) showed specific immunostaining in all 4 rhabdomyosarcomas included in this study. Anti-epithelial membrane antigen immunoreactivity was positive in all small-cell carcinomas of the lung. Anti-leukocyte common antigen (Dako) showed positive immunostaining in lymphomas and did not immunoreact with nonhematopoietic tumors. However, it was important to be aware that some lymphomas may not have been labeled with anti-leukocyte common antigen. All 6 neuroblastomas showed a positive immunoreactivity with anti-chromogranin A (LK2H10) and a weak reaction with antisynaptophysin (SY38). Panels of commercially available monoclonal antibodies, including anti-leukocyte common antigen, anti-epithelial membrane antigen, antidesmin (Dako), anti-muscle actin, and anti-chromogranin A, appear to be most useful in the differential diagnosis and staging of small round cell tumors on routinely processed biopsy specimens.

Actins↗
PubMed1988

Prenatal and perinatal risk factors for neuroblastoma. A case-control study.

Neuroblastoma is the most common neoplasm in children less than 1 year of age and has one of the earliest incidence peaks of all childhood cancers. Using birth registration data, a matched case-control study was undertaken to investigate potential prenatal and perinatal risk factors. Ninety-seven neuroblastoma patients who were born in Minnesota were matched with four controls each. No associations were identified for sex, race, parental age, parental education, complications of pregnancy, labor, or delivery, or the previously reported factors of birth weight greater than 4000 g or gestational duration of 36 weeks or less. In 6.6% of the cases and 0.8% of the controls, physical anomalies were noticed before discharge from the newborn nursery. Of the six anomalies reported in the cases, four were found to be the tumor itself or a complication of it. A significant protective effect (odds ratio (OR), 0.47) was noticed for a maternal history of previous fetal loss. Future studies, including biologic markers and stage stratification, may yield more insight into the cause of this disease.

Age Factors↗
PubMed1988

No involvement of bovine leukemia virus in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine lymphosarcoma. Much speculation continues to be directed at the role of BLV in human leukemia. To test this hypothesis rigorously, a case-control study of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma was conducted between December 1983 and February 1986. Cases (less than or equal to 16 years at diagnosis) derived from patients diagnosed at the primary institutions and affiliated hospitals were matched (age, sex, and race) with regional population controls. DNA samples from bone marrow or peripheral blood from 157 cases (131 acute lymphoblastic leukemia, 26 non-Hodgkin's lymphoma) and peripheral blood from 136 controls were analyzed by Southern blot technique, under highly stringent conditions, using cloned BLV DNA as a probe. None of the 157 case or 136 control DNA samples hybridized with the probe. The high statistical power and specificity of this study provide the best evidence to date that genomic integration of BLV is not a factor in childhood acute lymphoblastic leukemia/non-Hodgkin's lymphoma.

Adolescent↗
PubMed1988

Inoperable plasma cell granuloma of the heart: spontaneous decrease in size during an 11-month period.

Plasma cell granuloma occurs in children, typically as an intrapulmonary mass. Surgical excision is the treatment of choice and is usually curative. We report an atypical and unresectable plasma cell granuloma that occurred asymptomatically in the heart of a child and spontaneously decreased in size by 40% during an 11-month period. Thus, plasma cell granuloma should be considered in the differential diagnosis of any child who has a cardiac mass. Observation should be considered a treatment option because this case demonstrated that the cardiac mass can spontaneously recede without therapy.

Cardiomyopathies↗
PubMed1988

Idiopathic arterial calcification of infancy with unusual clinical presentations in sisters.

Two cases of idiopathic arterial calcification of infancy that occurred in sisters are reported. One patient died at age 14 months after a protracted course characterized by the nephrotic syndrome, blood chemistry abnormalities, hypertension, seizures, and a microangiopathic hemolytic anemia. Her sister died at age 3 weeks after a precipitous illness that initially was misinterpreted at autopsy as Reye's syndrome.

Calcinosis↗
PubMed1987

Acute lymphocytic leukemia: correlation of clinical features with immunocytochemical classification.

Many immunologic studies of acute lymphocytic leukemia (ALL) during the past decade have demonstrated the close correlation of immunologic phenotypes of ALL subclasses with the clinical presenting features and prognosis. However, the clinical application of conventional immunologic techniques had been very limited because of the requirement of a fresh sample to prepare the mononuclear cell suspensions for study. We studied 81 cases of ALL using immunoperoxidase stain for nuclear terminal deoxynucleotidyl transferase (TdT) and immunoalkaline phosphatase stain for surface markers (using monoclonal antibody J5 for common ALL antigen [CALLA], Leu-1 for pan-T antigen, and B1 for pan-B antigen) on air-dried smears. The cases were classified as common ALL (TdT+, CALLA+, pan-T-, and pan-B-) (41 cases), null-ALL (TdT+, CALLA-, pan-T-, and pan-B-) (19 cases), T-ALL (TdT+, CALLA-, pan-T+, and pan-B-) (nine cases), B-ALL (TdT-, CALLA-, pan-T-, and pan-B+) (six cases), pre-B-ALL (TdT+/-, CALLA+, pan-T-, and pan-B+) (four cases), or pre-T-ALL (TdT+, CALLA+, pan-T+, and pan-B-) (two cases). This subtyping of ALL correlated well with known clinical presenting features, prognosis, chromosome analysis in 35 cases with an abnormal clone, and conventional immunologic typing in 38 cases. The data suggest that these simple and practical immunocytochemical stains can be used for immunologic subclassification of ALL.

Chromosome Aberrations↗
PubMed1987

Left atrial mass 16 years after radiation therapy for mediastinal neuroblastoma.

Tumors involving the heart during childhood are rare. However, neuroblastoma, a common pediatric malignancy, has been described to involve the cardiovascular system in 3%-12% of patients dying with this tumor. Rarely is such involvement diagnosed ante mortem and never, to our knowledge, has a benign cardiac tumor been reported to present in childhood after successful eradication of neuroblastoma. We describe the identification and surgical resection of a nodular, hypertrophied, calcified, pedunculated left atrial mass in a 16-year-old boy who was complaining of exercise-associated presyncope and headaches 16 years after irradiation and chemotherapy for mediastinal neuroblastoma.

Adolescent↗
PubMed1987

Birth weight as a risk factor for childhood acute lymphoblastic leukemia.

Increased birth weight previously has been reported to be associated with childhood acute leukemia although the etiologic importance of this finding remains unclear. To further assess birth weight and associated parameters as a risk factor for childhood leukemia, a case/control study was performed using children with acute lymphoblastic leukemia (ALL) born in the state of Minnesota and diagnosed since 1969. Data obtained from birth registrations of 219 cases were compared with two control groups matched on date and county of birth (group I) or year of birth (group II). No significant differences were observed in mean birth weights of cases and controls. Statistically significant associations with birth weights greater than 3800 g were identified in cases diagnosed within the first 4 years of life. No associations were found between birth weight and ALL for case children diagnosed after 4 years of age. Factors that might be associated with increased birth weight, including maternal age, birth order, length of gestation, and socioeconomic status as measured by paternal education, were not found to be associated with an increased risk for ALL. The significance of the finding of high birth weight as a risk factor for childhood ALL remains unknown but suggests that pregnancy-related events may be of importance in the etiology of ALL in young children.

Birth Weight↗
PubMed1985

Pediatric phase I trial and pharmacokinetic study of tiazofurin (NSC 286193).

Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), a new nucleoside antimetabolite, was evaluated in a phase I trial involving children with refractory cancers. The drug was administered i.v. as a 10-min infusion daily for 5 consecutive days repeated at 3-week intervals. The dose ranged from 550 to 3300 mg/sq m/day. Seventeen patients received 23 courses and were evaluable for toxicity. The maximally tolerated dose was 2200 mg/sq m/day. The major dose-limiting toxicities were nonhematological. Neurotoxicity, including headache, drowsiness, and irritability, was common and was the principal dose-limiting toxicity at the higher doses. Severe myalgias were also dose limiting in one patient. Other side effects were mild, reversible elevations in serum transaminases; nausea, vomiting, and diarrhea; mild hypertension; dysphagia; and exfoliative dermatitis of the hands and feet. Myelotoxicity was not significant. The pharmacokinetics of tiazofurin was studied in 16 patients. Plasma disappearance was triphasic with half-lives of 9.7 min, 1.6 h, and 5.5 h. Clearance was dose related, ranging from 120 ml/min/sq m at 550 mg/sq m/day to 70 ml/min/sq m at 3300 mg/sq m/day. The primary route of elimination was renal with 85% of the drug recoverable in the urine as the parent compound in the 24 h following administration.

Adolescent↗