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Biomedical subjects

L L Robison

Publications and source records attributed to L L Robison.

At least 109 records · Page 6Linked to original sources
PubMed1991

Therapeutic radiation at a young age is linked to secondary thyroid cancer. The Late Effects Study Group.

We estimated the risk of thyroid cancer among 9170 patients who had survived 2 or more years after the diagnosis of a cancer in childhood. As compared with the general population, patients had a 53-fold increased risk (95% confidence interval, 34-80). Risk increased significantly with time since treatment for the initial cancer (P = 0.03). Detailed treatment data were obtained for 23 cases and 89 matched controls from the childhood cancer cohort. Sixty-eight % of the thyroid cancers arose within the field of radiation. Radiation doses to the thyroid of greater than 200 cGy were associated with a 13-fold increased risk (95% confidence interval, 1.7-104). The risk of thyroid cancer rose with increasing dose (P less than 0.001), but this was derived almost entirely from the increase from less than 200 to greater than 200 cGy. The risk of thyroid cancer did not decrease, however, at radiation doses as high as 6000 cGy.

Adolescent↗
PubMed1991

Intellectual function in long-term survivors of childhood acute lymphoblastic leukemia: protective effect of pre-irradiation methotrexate? A Childrens Cancer Study Group study.

Having demonstrated in a laboratory model that the neurotoxicity of CNS irradiation can be ameliorated with pre-irradiation methotrexate, we retrospectively compared two methods of CNS prophylaxis in childhood acute lymphoblastic leukemia which differed only in the timing of intrathecal methotrexate and radiotherapy. The results of standard IQ tests conducted 2-11 years after 24 Gy of cranial radiotherapy were obtained in 72 patients, of whom 27 had pre-irradiation methotrexate and 45 did not (control group). The two groups were otherwise comparable. In girls, the full-, performance-, and verbal-scale IQ scores were consistently higher in the pre-irradiation methotrexate group than in the corresponding control group (P less than 0.025). Among girls less than 5 years of age when irradiated, the mean IQ scores were 25-29 points higher after pre-irradiation methotrexate than after the control treatment (P less than 0.0007). These results suggest that pre-irradiation methotrexate may help prevent CNS radiotoxicity in children, and that the benefit is dependent on patient age and gender.

Asparaginase↗
PubMed1990

Wilms' tumor and paternal occupation.

A case-control study was conducted to examine the relationship between Wilms' tumor and paternal occupational exposures. The case group consisted of 200 children diagnosed as having Wilms' tumor who were registered at selected National Wilms' Tumor Study institutions during the period June 1, 1984, to May 31, 1986. Disease-free controls were matched to each case using a random digit dialing procedure. The parents of cases and controls completed a self-administered questionnaire. There was no consistent pattern of increased risk for paternal occupational exposure to hydrocarbons or lead found in this study. However, certain paternal occupations were found to have an elevated odds ratio (OR) of Wilms' tumor, including vehicle mechanics, auto body repairmen, and welders. Offspring of fathers who were auto mechanics had a 4- to 7-fold increased risk of Wilms' tumor for all 3 time periods. The largest increased odds ratio for auto mechanics was in the preconception period [OR = 7.58; 95% confidence interval (CI) = 0.90-63.9]. Welders had a 4- to 8-fold increased odds ratio, with the strongest association during pregnancy (OR = 8.22; CI = 0.95-71.3). Although chance cannot be excluded as a possible explanation, association of Wilms' tumor with these occupations has been reported in previous studies. Further study is needed to provide data on the specific occupational exposures involved.

Boron↗
PubMed1990

Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Children Cancer Study Group.

Testicular function was evaluated in 60 long-term survivors of childhood acute lymphoblastic leukemia (ALL). All the patients were treated on two consecutive Children Cancer Study Group protocols and received identical chemotherapy and either 18 or 24 Gy radiation therapy (RT) to one of the following fields: craniospinal plus 12 Gy abdominal RT including the gonads (group 1); craniospinal (group 2); or cranial (group 3). The median age at the time of their last evaluation was 14.5 years (range, 10.5 to 25.7), which took place a median of 5.0 years (range, 1 to 10.3) after discontinuing therapy. The incidence of primary germ cell dysfunction as judged by raised levels of follicle-stimulating hormone (FSH) and/or reduced testicular volume was significantly associated with field of RT; 55% of group 1, 17% of group 2, and 0% of group 3 were abnormal (P = .002). Leydig cell function, as assessed by plasma concentrations of luteinizing hormone (LH) and testosterone, and pubertal development, was unaffected in the majority of subjects regardless of RT field. These data indicate that in boys undergoing therapy for ALL, germ cell dysfunction is common following testicular irradiation and can occur following exposure to scattered irradiation from craniospinal RT. In contrast, Leydig cell function appears resistant to direct irradiation with doses as high as 12 Gy.

Adolescent↗
PubMed1990

Screening for neuroblastoma at 3 weeks of age: methods and preliminary results from the Quebec Neuroblastoma Screening Project.

A large neuroblastoma screening study was recently started in the province of Quebec, Canada. This project, a collaboration between the Quebec Network for Genetic Medicine and the University of Minnesota, is studying the impact of screening infants for the preclinical detection of neuroblastoma on the population-based mortality caused by this tumor. All infants born in Quebec during a 5-year period will be screened twice, at 3 weeks and at 6 months. Urinary homovanillic acid and vanillylmandelic acid determination from dried filter paper samples is used for screening. Initial qualitative screening is done by means of thin-layer chromatography with confirmatory quantitative screening by gas chromatography-mass spectrometry (GC-MS). During the initial 6 months of 3-week screening, 41,673 neonates (92% compliance rate) were screened and 10.6% of them were tested also by GC-MS. Nine of these neonates had positive results on two GC-MS tests and were referred for evaluation to rule out the presence of neuroblastoma. Four had the tumor, 1 had a calcified adrenal gland, and 4 had no tumor detected. Three additional neonates had clinical diagnosis of neuroblastoma before they reached the screening age of 3 weeks. A neuroblastoma that did not secrete homovanillic acid or vanillylmandelic acid was diagnosed clinically in 1 additional patient who tested negative by screening.

Chromatography, Gas↗
PubMed1990

Thyroid dysfunction following bone marrow transplantation: long-term follow-up of 80 pediatric patients.

Thyroid function was evaluated in children surviving disease-free for 2 years or more following bone marrow transplantation (BMT) for severe aplastic anemia (27 patients), acute non-lymphoblastic leukemia (28 patients), and acute lymphoblastic leukemia (25 patients). Pre-BMT conditioning consisted of high dose chemotherapy and total lymphoid irradiation with 750 cGy for patients with severe aplastic anemia, and for patients with leukemia, high dose chemotherapy and single dose total body irradiation with 750-850 cGy (33 patients) or fractionated total body irradiation with 1320 cGy (20 patients). Compensated hypothyroidism (elevated thyroid stimulating hormone (TSH) with a normal thyroxine index) occurred in 20/80 patients with a median time of onset of 12.3 months post-BMT (range 4-30). No patients developed primary hypothyroidism (elevated thyroid stimulating hormone with low thyroxine index). In seven patients, compensated hypothyroidism was transient with TSH returning to normal at a median of 60 months post-BMT (range 11-75). Six patients with compensated hypothyroidism received thyroid hormone replacement therapy. Time to development of compensated hypothyroidism was associated (p = 0.03) with underlying disease and radiation (11 of 27 patients with severe aplastic anemia + total lymphoid irradiation versus nine of 53 patients with leukemia + total body irradiation). In aplastic anemia patients, but not patients with leukemia, the incidence of thyroid hypofunction 5 years post-transplant was significantly higher (p less than 0.001) in those receiving methotrexate alone (82%) as prophylaxis for graft-versus-host disease compared with those receiving a regimen of methotrexate, antithymocyte globulin and prednisone (16%).

Adolescent↗
PubMed1989

Refractory anemia with excess of blasts in transformation hematologic and clinical study of 52 patients.

This study consists of 52 patients whose blood and bone marrow findings fulfilled the French-American-British (FAB) Cooperative Group criteria for a diagnosis of refractory anemia with excess of blasts in transformation (RAEB-T). The basis for the diagnosis of RAEB-T included 37 patients (71%) meeting one criterion, 13 patients (25%) meeting two criteria, and two patients (4%) meeting three criteria; 44% met only the criterion of the detection of Auer rods. Clonal chromosome abnormalities were seen in seven of 16 cases studied and included abnormalities of chromosome 5, an extra 8, and complex abnormalities. Thirty-one patients were treated with a chemotherapeutic regimen that included an anthracycline and cytarabine; 13 of 17 patients (77%) 45 years of age or younger and six of 14 patients (43%) over 45 years of age achieved CR. The median survival for the 17 patients 45 years of age or younger is 25+ months; the median survival for the 14 patients over 45 years of age is 12.3 months. The median survival for 13 untreated patients over the age of 45 is 4.5 months. The process in 18 of the 52 patients (35%) evolved to overt acute myeloid leukemia (AML) in 1 to 38 months after diagnosis of RAEB-T, in seven of 20 patients (35%) 45 years of age or younger, and 11 of 32 patients (34%) over 45 years. Fifteen of the 18 patients received antileukemic therapy in the RAEB-T phase. There were no clinical or laboratory features that were reliably predictive of transformation to AML.

Adolescent↗
PubMed1989

Occupational exposures of parents of children with acute nonlymphocytic leukemia: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group conducted a case-control study of occupational exposures of parents of 204 children (under 18 yr of age) with acute nonlymphoblastic leukemia. The most consistent finding was an association of acute nonlymphoblastic leukemia risk with pesticide exposure. Controls matched by date of birth and race were obtained through random digit dialing. Odds ratio (OR) for paternal pesticide exposure in jobs held for longer than 1000 days was 2.7 (95% confidence interval, 1.0 to 7.0; trend, P = 0.06), and seven case mothers and no control mothers had prolonged exposure (trend, P = 0.008). Risk estimates for parental pesticide exposure were substantially increased for children under age 6 at diagnosis (OR for prolonged exposure to either parent = 11.4; trend, P = 0.003) and for those with myelomonocytic and monocytic subtypes (OR, 13.6; trend, P = 0.007). Moreover, there were significantly elevated risks for direct exposure of the child to pesticides in the household (OR for exposure most days = 3.5; trend, P = 0.04) and for maternal exposure to household pesticides at the time of pregnancy (eight case mothers versus no controls for exposure most days; trend, P = 0.05). Paternal exposures to solvents (OR, 2.1; P = 0.003) and petroleum products (OR, 2.4; P = 0.002) were reported more commonly for cases than controls. Other occupational exposures reported significantly more often by case parents were paternal exposure to plastics or lead and maternal exposure to paints and pigments, metal dusts, and sawdust. These data provide further evidence for a role of occupational risk factors in the etiology of childhood cancer.

Adolescent↗
PubMed1989

Maternal drug use and risk of childhood nonlymphoblastic leukemia among offspring. An epidemiologic investigation implicating marijuana (a report from the Childrens Cancer Study Group).

The Childrens Cancer Study Group conducted a case-control study designed to assess in utero and postnatal exposures in children with acute nonlymphoblastic leukemia (ANLL). Analyses were performed for reported maternal use of medications and drugs in the year preceding and during the index pregnancy of the 204 case-control pairs. An 11-fold risk (P = 0.003) was found for maternal use of mind-altering drugs just prior to or during the index pregnancy. Compared with ANLL cases not exposed to marijuana, exposed cases were significantly younger at diagnosis of ANLL (P less than 0.01) and were more often of the myelomonocytic and monocytic subtypes (P less than 0.01). Use of antinausea medication for more than 11 weeks was also associated with a significantly elevated relative risk of 2.81 and a dose-response relationship was noted (P = 0.05 for trend). These results suggest that maternal drug use of marijuana may have an etiologic role in childhood ANLL and may be specific for morphologically defined subgroups.

Adolescent↗
PubMed1989

Growth in children following irradiation for bone marrow transplantation.

Longitudinal height data from 46 pediatric bone marrow transplant (BMT) patients, including 18 with aplastic anemia (AA), 19 with acute nonlymphoblastic leukemia (ANLL), and 9 with acute lymphoblastic leukemia (ALL), were analyzed to assess growth posttransplantation. Patients were prepared for BMT with high-dose cyclophosphamide followed by 7.5 Gy single-dose irradiation; AA patients received total lymphoid irradiation (TLI), and leukemia patients received total body irradiation (TBI). AA patients demonstrated reduced height posttransplant as reflected in a negative mean standard deviation score. The observed reduction was statistically significant only at 3 years following transplant. In contrast, leukemia patients showed a significant loss in relative height that was first visible at 1 year post-BMT and continued until at least 4 years post-BMT. Mean growth velocities in the leukemia patients were significantly below median for the 3 years following transplant. With a median follow-up of 4 years, antithymocyte globulin plus steroids in combination with methotrexate as graft vs. host prophylaxis was associated with less severe growth suppression than methotrexate alone, while there were no significant associations between growth during the first 2 years following transplant and prepubertal status at transplant (as defined by age), graft vs. host disease, thyroid or gonadal function, or previous therapies received by the leukemia patients. Children undergoing marrow transplantation, particularly those receiving TBI, are at significant risk of subsequent growth suppression.

Adolescent↗
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

Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus.

We studied the effect of successful pancreas transplantation and consequent normoglycemia (mean total hemoglobin A1, 7.0 percent; range, 5.8 to 8.3) on visual function and diabetic retinopathy in 22 patients with Type I diabetes mellitus (study group). Sixteen similar patients in whom pancreas transplantation had been unsuccessful (mean total hemoglobin A1, 12.0 percent; range, 8.0 to 18.0) served as a control group. The majority of patients in both groups had advanced proliferative retinopathy. At a mean follow-up of 24 months we found no significant difference between the groups in the rate of progression of retinopathy, expressed as a score. Success of the transplantation did not prevent progression of retinopathy across the range of retinopathy studied. Progressive retinopathy was observed more commonly in patients with low retinopathy scores (nonproliferative or mild proliferative retinopathy) at base line in both the study group (13 of 17 eyes, or 76 percent) and the control group (7 of 12 eyes, or 58 percent). Further analysis suggested the possibility that after three years of euglycemia, the study group had less deterioration than the control group, particularly in eyes with advanced retinopathy. We observed no difference in the rate of loss of vision between the two groups. This study provides evidence that pancreas transplantation and subsequent normoglycemia neither reverse nor prevent the progression of diabetic retinopathy.

Adolescent↗
PubMed1988

Epidemiology of the childhood acute leukemias.

Epidemiologic studies of the childhood leukemias have provided information relevant to several aspects of the care and follow-up of these children. The observations made regarding in utero radiation and ALL risk have certainly curtailed the use of routine obstetric diagnostic radiographs; observations regarding the association between birth weight, fetal loss, and other gestational events provide added enthusiasm for further research into basic biologic events occurring during fetal development; and the genetic patterns of disease supply critical information for genetic counseling and follow-up of affected patients and families. Additionally, the continued epidemiologic surveillance of children with cancer serves to form the foundation from which we will assess any future changes in childhood cancer incidence or pattern. Although not discussed here, the epidemiology of late effects, including second malignancies, reproductive function, and neuropsychologic functioning will assume a more prominent role as more children survive ALL and move into adulthood. While analytic studies have yet to yield an association as strong as the lung cancer/cigarette association in adults, future research designed to isolate biologically homogeneous disease populations for study may lead us to new and important associations. The continued cooperation of large pediatric oncology groups and private physicians is crucial as these future investigations are undertaken.

Acute Disease↗
PubMed1988

Kidney size at diagnosis of childhood acute lymphocytic leukemia: lack of prognostic significance for outcome.

The prognostic significance of kidney size at diagnosis of acute lymphoblastic leukemia (ALL) was assessed in a population of 142 children. Kidney size was determined using three different methodologies, and its significance was determined by univariate and multivariate life-table methods. Enlarged kidney size (as determined by any of the three methods used) was not associated with an overall poorer survival. These findings were consistent when kidney size at diagnosis was analyzed as a singled variable and when it was considered after adjustment for the known prognostic factors of age, sex, and initial WBC count. Assessment of renal size at the time of diagnosis of childhood ALL is not indicated for the purpose of predicting subsequent prognosis.

Age Factors↗