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Biomedical subjects

A T Meadows

Publications and source records attributed to A T Meadows.

At least 109 records · Page 6Linked to original sources

Medical and drug risk factors associated with neuroblastoma: a case-control study.

A matched case-control study of prenatal risk factors for neuroblastoma was conducted, including 104 cases diagnosed over the period 1970-79 in the Greater Delaware Valley. Significantly elevated odds ratios (ORs) were associated with maternal use of a neurally active drug during pregnancy (OR = 2.83), sex hormone exposure 3 months prior to or during pregnancy (OR = 2.25), frequent alcohol consumption during pregnancy (OR = 9.0), and maternal use of diuretic drugs during pregnancy (OR = 5.75). Significantly more case mothers than control mothers reported use of hair coloring products during pregnancy (OR = 3.0). No association was found between cigarette smoking, coffee consumption, or medical irradiation and case-control status.

Alcohol Drinking↗

The medical consequences of cure.

As more children are now being cured of cancer, increasing attention needs to be focused on the long-term sequelae of cancer therapy, principally late-appearing second cancers and damage to organ systems. To this end, the authors have established an oncology follow-up clinic specifically designed to examine former pediatric cancer patients who are likely to be cured. Patients receive a physical examination and appropriate organ function studies based upon initial diagnosis, pre-existing conditions, treatment received, and any complications experienced during the course of therapy. The late effects noted among the first 200 such survivors examined reveal a high proportion of severe sequelae secondary to radiation therapy in early childhood. Second malignant neoplasms may also be related to alkylating agent chemotherapy and to genetic conditions. Although certain therapeutic practices have improved the outlook for these patients, and, in some cases, reduction in intensity of therapy has been found to be effective, increased survival and newer treatment modalities have made extended follow-up increasingly necessary in order to detect and possibly prevent the occurrence of such late effects.

Antineoplastic Agents↗

Childhood neurofibromatosis: risk factors for malignant disease.

Forty-five children with both neurofibromatosis and malignant tumors were compared with a pediatric population with neurofibromatosis without tumors to ascertain if any of the clinical manifestations of this disorder were associated with either tumor development or histology. No such factors emerged except that, in most of the optic glioma patients, the neurofibromatosis mutation was paternally inherited. Concordance of histologic tumor types was seen when malignancies occurred in affected family members, similar to that noted in the literature. Although cancer is independent of the other manifestations of neurofibromatosis and these manifestations may vary among family members, it appears that malignant tumors are often concordant when they occur within a family.

Brain Neoplasms↗

Questionnaire study of cancer etiology in 503 children.

Usefulness of an etiologic questionnaire was examined in an interview study of 503 children with cancer. The medical records of the children were abstracted, and their parents responded to a questionnaire-interview to identify genetic and environmental causes of cancer. Among 1,123 siblings of the index patients, 10 developed cancer as compared with 2 expected on the basis of cancer rates for the general population. Cancer risk factors were identified in individual patients with predisposing genetic and congenital disorders: neurofibromatosis (brain tumor), hereditary immunodeficiency (lymphoma), Down's syndrome (leukemia), XY gonadal dysgenesis (germ cell tumor), giant nevus (melanoma), and meningocele (sacral teratocarcinoma). Environmental causes of childhood cancer were difficult to discern because prior exposures were numerous, diverse, and usually ill defined. The questionnaire yielded more data than the medical record on gestational and family history and helped identify patients with exceptionally high cancer risk for additional investigation. Although the findings provide anecdotal confirmation of several associations, few original etiologic hypotheses were generated for formal testing with conventional epidemiologic techniques.

Adolescent↗

Gonadal effects of cancer therapy in boys.

A retrospective study of testicular histology was carried out in 21 prepubertal boys and in 11 intrapubertal or postpubertal boys who died from 1 day to 1 year after treatment with chemotherapy (CT) with or without radiation therapy (RT) for extragonadal solid tumors. Based on autopsy findings, profound histologic changes were found in six prepubertal boys and in all but one of the intrapubertal and postpubertal boys. For three of the prepubertal and five of the postpubertal boys with altered testicular histology, the contribution of pelvic RT could not be excluded. When prepubertal patients were evaluated according to nutritional status, a thickened tubular wall and absent or severely reduced spermatogonia were found in only 1 of 11 adequately nourished boys as compared with 5 of 10 malnourished boys. In intrapubertal and postpubertal boys, the tubular wall was thickened in six and these changes were independent of nutritional status. All malnourished intrapubertal and postpubertal patients demonstrated impaired spermatogenesis (versus 67% of age-matched malnourished controls), whereas similar impairment was noted in 60% with adequate nutrition versus 20% of controls. The diffuse damage of germ cells and tubules in malnourished younger boys suggests that the prepubertal male is not necessarily protected against the reproductive effects of cancer therapy.

Adolescent↗

Gonadal effects of cancer therapy in girls.

The gonadal histology of 21 prepubertal, intrapubertal, and postpubertal girls who died 1 day to 2 months after cessation of therapy for extragonadal solid tumors was reviewed. In addition to focal or diffuse cortical fibrosis, a reduction in follicle numbers and impaired follicular maturation were observed in cancer patients independent of their pubertal age. These changes appeared to be more severe in malnourished patients and in girls who received multiple agent chemotherapy, with or without irradiation. Both before and after the age of 10 years, most cancer patients had a total number of follicles similar to that of age- and nutrition-matched controls. However, the majority of these girls displayed impaired follicular maturation as demonstrated by reduced numbers of growing and antral follicles compared to controls. Histologic evidence of ovarian damage suggests that the future reproductive performance may be impaired in some female cancer patients treated even before puberty.

Adolescent↗

Syndrome of inappropriate antidiuretic hormone secretion. A complication of high-dose intravenous melphalan.

Melphalan is now being investigated as an intravenous (IV) bolus chemotherapeutic agent in children with resistant tumors involving the bone marrow. Two patients received 2 mg/kg melphalan, IV bolus; 10 patients received 1 mg/kg. Seven of the ten patients receiving 1 mg/kg had noticeable downward trends in the serum sodium concentrations, whereas both patients receiving 2 mg/kg developed hyponatremia (serum sodium concentration [SNa], mEq/l = 124-125) and inappropriate urinary sodium losses. Syndrome of inappropriate antidiuretic hormone (SiADH) is a previously unreported complication of high dose bolus melphalan therapy.

Adolescent↗

Height of children successfully treated for acute lymphoblastic leukemia: a report from the Late Effects Study Committee of Childrens Cancer Study Group.

One hundred eighty-seven patients diagnosed with acute lymphoblastic leukemia (ALL) between 1972 and 1975 were evaluated for height 6.4-8.8 years (median 7.2 years) from the time of diagnosis of their disease. All patients had been treated on protocols CCG-101/143 conducted by the Childrens Cancer Study Group. After induction of remission, patients received either cranial radiation plus six doses of intrathecal methotrexate, craniospinal radiation, or craniospinal radiation plus abdominal radiation, followed by systemic maintenance chemotherapy for either 3 or 5 years. No significant difference was observed in the distribution of height percentiles at the time of diagnosis compared to expected population standards. After treatment an excess (P less than 0.001) was observed in the proportion of patients in the lower percentiles in conjunction with a decrease in the proportion of patients in the higher percentiles. After adjustment for height at diagnosis, the only factor found to have significant impact on attained height percentile was exposure to craniospinal plus abdominal radiation (P less than 0.001) where there was a fivefold excess in the proportion of patients below the fifth percentile for height. Craniospinal radiation only was not associated with a greater reduction in attained height percentile when compared to cranial radiation only.

Adolescent↗

Second malignant neoplasms in children: an update from the Late Effects Study Group.

This paper presents an update from the Late Effects Study Group on 292 cases of second malignant neoplasms (SMN) occurring in individuals who were diagnosed with their first neoplasm in childhood. Data are presented regarding the types of first and second neoplasm, the therapy administered, and the predisposing factors. Of the 292 cases (308 SMN), the most common primary was retinoblastoma followed by Hodgkin's disease, soft-tissue sarcomas, and Wilms' tumor. This is not similar to the relative frequency of these cancers in children but rather reflects specific risk factors. Bone sarcomas were the most common SMN among the 208 SMN developing in previously irradiated sites while acute leukemia was the most common SMN unassociated with radiation. Known predisposing conditions to cancer were present in 73 cases; retinoblastoma was the most common of these, followed by neurofibromatosis. There were ten patients with three and three patients with four malignant neoplasms. In 14 patients, the cause of SMN was not suggested by known risk factors as these patients had negative family histories and received no radiation or chemotherapy. We note, therefore, that although most cases of SMN in survivors of childhood cancer can be attributed to radiation, genetic disease, chemotherapy, or combinations of these, unrecognized predisposition or chance may also play a role.

Antineoplastic Combined Chemotherapy Protocols↗

Racial variation in incidence of Wilms' tumor: relationship to congenital anomalies.

This is a study of the occurrence of Wilms' tumor and associated anomalies in all incident cases in the Greater Delaware Valley by race. The average annual incidence of Wilms' tumor in this population of 2 million children is significantly higher among nonwhites than whites. A significantly larger proportion of black cases has a Wilms' tumor-associated condition including aniridia, genito-urinary anomalies, the Beckwith-Wiedemann Syndrome, and hemihypertrophy. For very young patients, there was a greater tendency for blacks to have bilateral tumors or a tumor-associated anomaly, features characteristic of the hereditary form of Wilms' tumor. The excess risk of Wilms' tumor among blacks may be a result of a higher proportion having a hereditary predisposition or more common exposure to agents capable of inducing germinal mutations.

Abnormalities, Multiple↗

An on-line interactive interviewing program for epidemiological studies.

An on-line interactive verification and entry system (OLIVES) has been developed for conducting telephone interviews in large-scale epidemiological studies. Responses are automatically coded into a computer legible form suitable for analysis. Use of a question stack to control question flow allows on-line response modification, restart from any termination point, and minimal reprogramming in order to change question order. Numerical, coded, and text string data types are permitted. A multilevel hierarchical data structure reflects interview content. The advantages and disadvantages of the on-line approach are discussed. OLIVES is generalizable and is applicable to other on-line or off-line interview situations.

Child↗

The efficacy of random digit dialing in selecting matched controls for a case-control study of pediatric cancer.

A study of random digit dialing as a method of control selection was conducted as part of a matched case-control study of risk factors for neuroblastoma. The study was conducted in 1981-1982 in the Greater Delaware Valley region. Participation involved parents submitting to a 2-4-hour telephone interview. Potential control telephone numbers were selected by substituting the last two digits of the case family's telephone number with randomly selected digits. Successive random telephone numbers were called until a family with a child matching the case by year of birth plus or minus three years and race who agreed to participate was identified. A total of 3,245 telephone numbers were dialed to select controls for 101 cases, an average of 32.1 telephone numbers per case. Among 1,908 residential households contacted, 25.5% refused to give information about household characteristics. Of households with known characteristics, 45% had children under 25 years of age and 14.9% had a child eligible for the study. Among 181 households invited to participate, 101 agreed. For 18.6% of all calls, residential respondents were randomly offered $10 as an inducement to participate. This inducement did not significantly influence participation rates among families invited to participate.

Adult↗

Factors associated with IQ scores in long-term survivors of childhood acute lymphoblastic leukemia.

To identify factors which might be associated with intellectual function following treatment for childhood acute lymphoblastic leukemia, 50 long-term survivors were studied using the Wechsler Intelligence Scale for Children-Revised. All patients were diagnosed between 1972 and 1974 and were treated on a single clinical trial protocol with identical induction and maintenance chemotherapy plus central nervous system prophylaxis that included cranial radiation. The mean full scale IQ score for the group was 95 (SEM 2.0), with mean verbal IQ of 94.4 and mean performance IQ of 96.9. Factors which were found to be closely associated with a lower IQ score included female sex (in both verbal IQ and full-scale IQ), longer duration of chemotherapy (in performance IQ), and younger age at the time of radiation (in both verbal IQ and full-scale IQ). The age at the time of radiation was found to be significantly correlated with discrepancy between verbal and performance IQ, with younger age being associated with verbal IQ scores higher than performance IQ scores. When analyses were performed within specific subgroups of patients defined by sex and age at the time of radiation, dose of cranial radiation, concomitant intrathecal methotrexate therapy, and duration of therapy were all found to be correlated with a lower level of intellectual function. These preliminary findings provide direction for future studies to help identify high-risk patients.

Adolescent↗

The treatment of localized non-Hodgkin's lymphoma in children: a report from the Children's Cancer Study Group.

Investigators of the Children's Cancer Study Group entered 73 children with previously untreated localized non-Hodgkin's lymphoma on a prospective randomized trial of systemic treatment with either a four-drug program (cyclophosphamide, vincristine, methotrexate, prednisone [COMP]) or a 10-drug (LSA2-L2 modified) program of 18 months duration. All patients received central nervous system prophylaxis with intrathecal methotrexate and most received local or regional radiation treatment. The three-year relapse-free survival rate for all patients (N = 73) was 84%; for COMP (N = 42) was 85%, and for LSA2-L2 (N = 31) was 84%. Of the 12 patients who suffered adverse events eight relapsed and four died of toxicity. Histopathology was reviewed centrally. Of 32 patients with nonlymphoblastic disease treated with COMP only one relapsed. Of 26 patients treated with LSA2-L2, four relapsed. Patients with localized lymphoblastic disease were uncommon. None of three patients treated with LSA2-L2 relapsed compared with three of nine treated with COMP. COMP is an excellent treatment for patients with localized disease of nonlymphoblastic type, but the relative value of the two regimens for patients with localized lymphoblastic disease is uncertain.

Adolescent↗

Influence of place of treatment on diagnosis, treatment, and survival in three pediatric solid tumors.

This study examines differences between cancer centers (CC) and noncancer centers (NCC) in terms of management procedures and outcomes for three pediatric solid tumors: Wilms' tumor (N = 147), rhabdomyosarcoma (N = 87), and medulloblastoma (N = 76). Data were derived for the period 1970-1979 from the population-based Greater Delaware Valley Pediatric Tumor Registry maintained at the Children's Cancer Research Center, which routinely collects data on all childhood neoplasms that occur in a 31-county region. Management measures reviewed included the degree to which important pretreatment evaluations were performed, types of therapy used, and extent of follow-up examinations conducted. Outcome variables were three-year disease-free survival and frequency of deaths related to complications of therapy. Differences in three-year disease-free survival between CC and NCC were noted for medulloblastoma (52% v 24%) and rhabdomyosarcoma (48% v 10%), but not for Wilms' tumor (79% v 68%). Among medulloblastoma patients, differences were detected in the frequency of pretreatment evaluations and in the therapy used. The principal management contrast found in rhabdomyosarcoma was that multiagent chemotherapy was used less often in NCC. Wilms' tumor patients were evaluated and treated similarly in the community versus the CC, except for some contrasts in the surgical approach and the frequency of follow-up for the detection of late complications.

Adolescent↗

Childhood non-Hodgkin's lymphoma. The results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2).

Members of the Childrens Cancer Study Group treated 234 eligible patients in a randomized trial designed to study the relative effectiveness of two therapy programs for the treatment of childhood and adolescent non-Hodgkin's lymphoma. Two chemotherapeutic strategies were compared: a 4-drug regimen (COMP) and a 10-drug regimen (modified LSA2-L2). Failure-free survival for all patients was 60 per cent at 24 months. In patients with disseminated disease treatment success was influenced by both the histologic subtype of disease and the therapeutic regimen followed. The 10-drug program was more effective than the 4-drug program in patients with disseminated lymphoblastic disease (two-year failure-free survival rate, 76 vs. 26 per cent, respectively; P = 0.0002), whereas the 4-drug program was more effective than the 10-drug program in those with nonlymphoblastic disease (57 vs. 28 per cent, respectively, P = 0.008). The less toxic, more easily administered 4-drug regimen was as effective as the 10-drug regimen in patients with localized disease (89 vs. 84 per cent, respectively).

Adolescent↗