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Biomedical subjects

D Fairclough

Publications and source records attributed to D Fairclough.

At least 55 records · Page 3Linked to original sources
PubMed1992

Use of GM-CSF in children after high-dose chemotherapy.

The toxicity and efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) is established in adults, but limited information is available on its use in children. The profound myelotoxicity induced by cisplatin (40 mg/m2 daily x 5) and etoposide (150 mg/m2 daily x 3) provides a model to test the clinical value of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric cancer patients; myelosuppression occurred (absolute neutrophil count [ANC] < 500/microL) during 99 of 118 (84%) courses given to 44 children with refractory solid tumors. Fifty-nine courses (50%) resulted in hospitalizations for fever. Subsequently, rhuGM-CSF was added to this treatment regimen to: (i) determine the dose-limiting toxicity of this agent in children; and (ii) to determine whether it can decrease the duration and severity of neurtropenia and attendant complications. Here we summarize and update our experience with this glycoprotein in children with relapsed solid tumors.

Adolescent↗
PubMed1992

Deterioration of intellect among children surviving leukemia: IQ test changes modify estimates of treatment toxicity.

This study assessed the association of young age at treatment, cranial irradiation, and time since treatment with intellectual deterioration among 49 long-term survivors of childhood leukemia. Ss had been randomized to receive low-dose cranial radiation therapy or high-dose chemotherapy. Longitudinal assessments of intellect were conducted. No significant effects of treatment group or age at treatment were detected. A small but statistically significant decline in mean full-scale IQ was noted over time (M = -3.6). Reanalysis with IQ test version included as a covariate eliminated IQ declines found initially. Results suggest (a) that there has been reduced toxicity of these methods of treatment and (b) that the magnitude and direction of error introduced by changing tests may approximate the magnitude of adverse effects on IQ from treatment.

Age Factors↗
PubMed1992

Long-term survivors of leukemia treated in infancy: factors associated with neuropsychologic status.

PURPOSE: Because of concerns about late toxicities of treatment among infants diagnosed with acute lymphoblastic leukemia (ALL), and especially the effects of cranial radiation therapy (CRT), we compared the functional and neuropsychologic status of 26 long-term survivors of ALL who were diagnosed in the first 24 months of life versus 26 children who were treated previously for Wilms' tumor. PATIENTS AND METHODS: Of the children with ALL, CNS prophylaxis included no CRT in six, 18 Gy CRT in five, 20 Gy CRT in seven, and 24 Gy CRT in five. Three additional children experienced CNS relapse and received total CRT doses of 24, 40, and 44 Gy. All children received neuropsychologic testing; children with ALL also participated in diagnostic imaging studies. RESULTS: As a group, the children who were treated for ALL did not differ significantly from those who were treated for Wilms' tumor on objective measures of global functional status. However, children treated for ALL had a significantly lower mean intelligence quotient (IQ) (87 v 96), poorer performance on four of six measures of visual and auditory memory, lower achievement with regard to arithmetic skills, and a greater frequency of special educational intervention than those who were treated for Wilms' tumor. IQ and auditory memory performance in the ALL group was correlated inversely with time since the completion of therapy and total CRT dose. CONCLUSIONS: These results reinforce the contemporary trend of prophylactic CRT omission in very young children except for those who are at risk for CNS relapse. For infants and very young children who require CRT, evidence is presented that supports the approach for the delay of CRT until the child is older.

Adolescent↗
PubMed1991

Midazolam premedication for pediatric bone marrow aspiration and lumbar puncture.

The ability of midazolam, a benzodiazepine, to reduce the distress associated with lumbar puncture and bone marrow aspiration was examined in 23 children with acute lymphocytic leukemia. Patients were randomized to receive 0.2 mg/kg midazolam HCl or placebo intravenously 3-5 min before the procedures, under double-blind conditions. Based on prior experiences, children in both groups anticipated severe pain from these procedures. Postprocedure pain ratings by patients were markedly reduced in the midazolam but not the placebo group. Both physicians and parents judged the midazolam group as significantly less distressed than controls during and after the procedures. Trained observers recorded significantly fewer pain- and anxiety-related behaviors in the midazolam group immediately before and after, but not during the procedures. The amnestic effects of midazolam, confirmed in a visual recall/recognition test, appear to account for the decreased pain ratings since the behavioral manifestations were similar in the two groups. There were no adverse drug reactions or significant changes in vital signs. Midazolam warrants further investigation as a premedication for painful diagnostic and treatment procedures in children with cancer.

Adolescent↗
PubMed1991

Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study.

We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function.

Adolescent↗
PubMed1991

A prospective comparison of neuropsychologic performance of children surviving leukemia who received 18-Gy, 24-Gy, or no cranial irradiation.

To compare the late neuropsychologic toxicities of CNS prophylaxis for childhood acute lymphoblastic leukemia (ALL), longitudinal assessments were performed on three groups of patients: those who received repeated courses of moderate-dose (1 g/m2) intravenous (IV) and intrathecal methotrexate (IT MTX) without cranial irradiation (MTX group, n = 26), those who received IT MTX and 18 Gy cranial irradiation (18-Gy group, n = 23), and those who received IT MTX and 24 Gy cranial irradiation (24-Gy group, n = 28). All patients were free of CNS leukemia at diagnosis and had remained in continuous, complete remission 5 to 11 years (median, 7.4 years) following CNS prophylaxis. An analysis of serial intelligence quotient (IQ), achievement, and neuropsychologic studies revealed no significant influence of either age at CNS prophylaxis or CNS prophylaxis group on any neuropsychologic outcome measure. After adjusting for changes in IQ test versions that were necessitated by advancing patient age, no statistically significant declines in Verbal, Performance, or Full Scale IQs were noted for the three CNS treatment groups. However, comparisons of group means masked declines in individual children; 22% to 30% of children exhibited a clinically significant deterioration (greater than or equal to 15 points) in uncorrected IQ values over the study period. Female sex was associated with an increased risk of deterioration in Verbal IQ, but we were unable to identify risk factors associated with other declines in intellect and achievement. The inability to reliably predict individual patients at risk for clinically significant neuropsychologic toxicities on the basis of age at diagnosis or specific method of CNS prophylaxis suggests that other etiologic factors must be explored as the basis for these changes, such as ecologic factors and chemotherapy during the continuation phase of treatment.

Adolescent↗
PubMed1991

Pleural effusion is associated with a poor treatment outcome in stage III small non-cleaved cell lymphoma.

The clinical significance of pleural effusion was assessed in 24 children with unresectable abdominal small non-cleaved cell lymphoma (St. Jude Stage III). Patients were consecutively enrolled and treated on a regimen including high dose fractionated cyclophosphamide and co-ordinated high dose methotrexate and cytarabine. The overall results were excellent, with 20 of 24 patients alive and event-free at a median follow-up of 4 years. Only one of the patients who lacked pleural effusion has relapsed (testicular), even though many had massive disease. In contrast, three of seven patients with pleural effusion have failed treatment (p = 0.02) and subsequently died. Two measures of tumor burden, serum lactic dehydrogenase and, in a subset of patients, interleukin-2-receptor levels, were significantly higher in patients with pleural effusion (p = 0.002 and p = 0.05, respectively). These findings suggest that unresectable abdominal small non-cleaved cell lymphoma associated with pleural effusion should be up-staged and that these patients should receive more intensive chemotherapy.

Abdominal Neoplasms↗
PubMed1990

Clinical and biological characteristics of acute lymphocytic leukemia in children with Down syndrome.

Twenty-eight children with Down syndrome (DS) and acute lymphocytic leukemia (ALL) were compared to non-DS control leukemics matched by age, white blood cell (WBC) count, and treatment protocol to evaluate presenting manifestations, toxicity, and outcome. The DS children with ALL did not have unique clinical or biologic characteristics to distinguish their disease from that of non-DS patients. Eleven of the DS patients had successfully banded cytogenetic studies of their leukemic cells with the distribution of model chromosome number of 46 (n = 1), 47 (2), 48 (5), and greater than 50 (3). The abnormal leukemic line involved an isochromosome of the long arm of chromosome 9[i(9q)] in 3 cases. Multiagent chemotherapies induced complete remissions in 25 patients (85%), yet overall 5 year event-free survival was only 23 +/- 8% when compared to 64 +/- 9% for control children receiving similar therapies (P less than 0.01). A significant cause of treatment failure was late marrow recurrence in the DS children. Host toxicity was striking in these children. Severe congenital heart disease present in one-third contributed to 2 deaths during antileukemia therapy. Hyperglycemia secondary to diabetogenic agents and repeated bronchitis were common toxicities. Intolerance to the antifolate methotrexate with severe gastrointestinal and skin toxicities was universal. We conclude that the poor prognosis for the child with DS and ALL stems in part from their increased risk of complications and toxicity from intensive modern leukemia therapies, specifically antifolates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A comparison of placement techniques and complications of externalized catheters and implantable port use in children with cancer.

The complications associated with the placement and use of Hickman catheters (n = 120), Broviac catheters (n = 146), and implantable ports (n = 93) in children with cancer were analyzed. Percutaneously placed central venous access devices (CVADs) tended to fail less often (P = .86) and to develop infections less often (P = .056) than surgically placed CVADs. The difference in complications with percutaneous versus surgically placed CVADs requires confirmation in a randomized trial to assure they are not a result of differences in patient characteristics. When all catheter failures (removal due to infection, obstruction, or dislodgement) were considered, ports had a significantly longer failure-free duration of use than externalized Hickman and Broviac catheters (P = .0009). Ports also remained infection-free longer than externalized catheters (P = .0014). The greatest risk of infection occurs in the first 100 days of use, particularly for ports. This study demonstrates that for long-term use (greater than 100 days) ports are superior to externalized catheters in children with cancer.

Bacterial Infections↗
PubMed1989

Effect of antioxidants in experimental Escherichia coli septicemia.

Free radicals have been implicated in the pathogenesis of gram-negative bacterial sepsis. We assessed the effectiveness of antioxidants and chelators to alter oxidative injury in established severe experimental Escherichia coli septicemia. One hour after challenge by intraperitoneal injection of bacteria, 36 rabbits were treated with moxalactam and randomized in sets of three to receive either placebo, superoxide dismutase (SOD), or a combination of antioxidants and chelators consisting of SOD, sodium thiosulfate, alpha-tocopherol, deferoxamine, and diethyldithiocarbamate. Throughout the course of treatment, levels of bacteremia and endotoxemia were similar among the three experimental groups. Neither antioxidant-treated group was significantly different from the control group in mean arterial blood pressure, leukocyte count, platelet count, core temperature, blood lactate, oxygenation or survival. Arterial pH and [HCO3-] were significantly lower in the antioxidant combination group compared to the control and SOD groups (P less than .01). In this model, antioxidant and chelator therapy does not substantially ameliorate established septicemia.

Animals↗
PubMed1989

Social competence and behavioral adjustment of children who are long-term survivors of cancer.

Relatively little is known about the special needs of long-term survivors of childhood cancer or the factors that make this growing population vulnerable to chronic psychologic disorders. We therefore surveyed 183 children who had been treated for cancer at St Jude Children's Research Hospital and were free of the disease for greater than or equal to 2 years after completing therapy. Parental responses to the Child Behavior Checklist, a standardized inventory of social competence and behavioral problems, were analyzed in relation to demographic and medical variables, as well as the children's appearance and functional status. School-related problems and somatic complaints of undetermined origin were increased fourfold relative to age- and gender-adjusted rates for peer groups in the general population. The presence of functional but not cosmetic impairments increased the risk of academic and adjustment problems. An older age at evaluation, treatment with cranial irradiation, and residence in a single-parent household were also associated with an increased risk of psychologic problems. General pediatricians must eventually assume responsibility for the extended follow-up care of children who have survived a malignancy. Their awareness of the high-risk groups described in this report should facilitate more timely identification of problems and referral of the children to appropriate services.

Achievement↗
PubMed1988

High-dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude Total Therapy Study X.

High-dose methotrexate (HDMTX, 1,000 mg/m2) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard-risk ALL: a leukocyte count less than 100 X 10(9)/L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone-vincristine-asparaginase induced complete remissions in 95% of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks. With a median follow-up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC (P = .049) or historical institutional control regimens (P = .002). Approximately 67% of the patients receiving HDMTX and 56% of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar (P = .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in children with ALL.

Child↗
PubMed1988

Reduced therapy for Wilms' tumor: analysis of treatment results from a single institution.

From 1968 to 1986, 192 patients from 0 to 17 years of age were enrolled in three consecutive protocol-controlled studies of Wilms' tumor at St Jude Children's Research Hospital. Tumors were completely excised at the time of diagnosis whenever possible, and patients were subsequently treated with chemotherapy and radiotherapy according to the initial extent of disease. All patients received dactinomycin and vincristine, with doxorubicin added to the regimens in studies 2 and 3. Chemotherapy was extended to 18 months in study 2 (n = 53), but was limited to 12 months for most patients in study 3 (n = 107). In the third study, radiation was eliminated altogether for patients with stage I or II tumors and was reduced to 12 Gy for those with more advanced disease. Intensification of chemotherapy in study 2 improved the 5-year relapse-free survival rate over that in study 1 (82% v 52%), but the accompanying increase in toxicity was considered unacceptable. Comparison of 2-year relapse-free survival rates in studies 2 and 3 indicated that the reduction of therapy in the latter trial did not jeopardize disease control: 88% v 86% for patients with stage II or III disease, favorable histology; 75% v 57% for the same stages, unfavorable histology; and 57% v 61% for stage IV patients. At least 80% of all patients enrolled in study 3 will be long-term survivors. We conclude that rescheduling of effective antitumor drugs and eliminating or reducing radiotherapy are feasible alternatives in the treatment of Wilms' tumor with favorable histologic features.

Adolescent↗
PubMed1988

Memory function in disease-free survivors of childhood acute lymphocytic leukemia given CNS prophylaxis with or without 1,800 cGy cranial irradiation.

Previous studies have found that CNS prophylaxis of children with leukemia, especially young children receiving cranial irradiation, causes neuropsychologic deficits. In the present study, 40 children in continuous complete remission from acute lymphocytic leukemia (ALL) were given a battery of tests to assess memory functioning 5 years after CNS prophylaxis. All children were free of CNS disease at diagnosis and had been randomly assigned to receive CNS prophylaxis with either 1,800 cGy cranial irradiation (CRT) plus intrathecal (IT) methotrexate (MTX) or IT MTX plus intravenous (IV) high-dose MTX (HDMTX). No treatment- or age-related differences were seen on 16 standardized memory measures. However, scores of the combined sample were significantly lower than age-corrected norms on a test of visual-spatial memory and on four scales of verbal memory. Differences in methods or intensity of CNS prophylaxis and study group selection criteria are proposed to explain our findings and to resolve discrepancies with previous reports. The long-term neuropsychological sequelae in these survivors of ALL may be attributable to some common factor, such as the disease itself or systemic and IT chemotherapy.

Child↗
PubMed1988

Spirometry and chest wall dimensions in achondroplasia.

Standard values for pulmonary function in short-limbed dwarfism are not available. Therefore, chest diameters and expiratory spirograms were measured in 58 female and 44 male subjects between 7 and 60 years of age with achondroplasia, the most common form of dwarfism. Standing height in adults was 49.6 +/- 3.2 (SD) inches with a sitting/standing height ratio of 0.66 (normal 0.52-0.53). Despite extremely short stature, only AP chest diameters in males were smaller than control subjects of similar age. The following equations were derived for forced vital capacity (FVC): males (under 25 years), FVC(L) = -3.56 + 0.162 X sitting height (in) + 0.067 X age (yrs); males (over 25 years), FVC(L) = -0.73 + 0.162 X sitting height (in) -0.047 X age (yrs); females (under 20 years), FVC(L) = -3.56 + 0.150 X sitting height (in) + 0.067 X age (yrs); females (over 20 years), FVC(L) = -1.92 + 0.150 X sitting height (in) -0.016 X age (years). Similar prediction equations were derived for FEV1 and FEF25-75%: FEV1/FVC % was 84.2 (+/- 6.5) for females and 88.0 (+/- 6.5) for males. We also compared the observed FVC measurements to values calculated using standing heights derived from the subject's sitting height, assuming a normal body proportion. The observed vital capacity in achondroplasia was only 67.6 (+/- 19.2) percent of that predicted for normally proportioned females and 72.4 (+/- 13.6) percent for males, suggesting reduced vital capacity in achondroplasia, due to reduced chest wall compliance or abnormal lung growth.

Achondroplasia↗