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Biomedical subjects

D Fairclough

Publications and source records attributed to D Fairclough.

At least 37 records · Page 2Linked to original sources
PubMed1996

Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary sarcomas.

BACKGROUND: An excess risk of second malignancies has been reported in survivors of Ewing's sarcoma. We examined a multiinstitutional data base to reevaluate the risk among survivors of Ewing's sarcoma and to identify possible causal factors. METHODS: Information was derived from a data base that included 266 survivors of Ewing's sarcoma. Cumulative incidence rates of second malignancies were calculated. Contributions of clinical features, type and dose of chemotherapy, and cumulative radiation dose to the risk of second malignancies were evaluated. RESULTS: After a median follow-up duration of 9.5 years (range, 3.0 to 30), 16 patients have developed second malignancies, which included 10 sarcomas (five osteosarcomas, three fibrosarcomas, and two malignant fibrous histiocytomas) and six other malignancies (acute myeloblastic leukemia, acute lymphoblastic leukemia, meningioma, bronchioalveolar carcinoma, basal cell carcinoma, and carcinoma-in-situ of the cervix). The median latency to the diagnosis of the second malignancy was 7.6 years (range, 3.5 to 25.7). The estimated cumulative incidence rates at 20 years for any second malignancy and for secondary sarcoma were 9.2% (SD = 2.7%) and 6.5% (SD = 2.4%), respectively. The cumulative incidence rate of secondary sarcoma was radiation dose-dependent (P = .002). No secondary sarcomas developed among patients who had received less than 48 Gy, while the absolute risk of secondary sarcoma was 130 cases per 10,000 person-years of observation among patients who had received > or = 60 Gy. CONCLUSION: The overall risk of second malignancies after Ewing's sarcomas is similar to that associated with treatment for other childhood cancers. The radiation dose-dependency of secondary sarcomas justifies modification in therapy to reduce radiation doses.

Adolescent↗
PubMed1995

Chemotherapy-induced nausea and emesis in pediatric cancer patients: an analysis of coping strategies.

We investigated the preference and perceived efficacy of coping strategies used to manage chemotherapy-induced nausea and emesis in 57 pediatric oncology patients. Over 85% of children preferred "Wishful Thinking," "Emotional Regulation," and "Distraction" to cope with nausea, and "Emotional Regulation" to manage emesis. Stepwise logistic regression analyses revealed that the coping strategy used and its perceived efficacy depended upon patient age and gender, severity of symptom distress, time elapsed from last chemotherapy, experience, and whether nausea or emesis was the identified problem. Successful copers, defined as those reporting high coping efficacy and minimal distress, composed only 25% of the sample. These children most often used "Problem Solving" combined with "Social Support" for symptom management. Successful coping was also associated with lower emetogenic potential of chemotherapy. The significance of these results is discussed for identifying high-risk children who may benefit from coping interventions.

Adaptation, Psychological↗
PubMed1995

Avoidant coping in children with cancer.

Compared coping styles in children with cancer (n = 66) and a normative control group of healthy children (n = 414), using a newly designed instrument, the Children's Behavioral Style Scale (CBSS). We hypothesized that children in the oncology group would make greater use of an avoidant coping style (blunting) than controls. Results confirmed the primary hypothesis; children with cancer endorsed greater use of blunting or avoidant coping than did healthy children. A new conceptual model of coping style was introduced utilizing CBSS scores to identify children as Monitors, Blunters, Active, or Passive copers. Using this model, a similar proportion of Active and Passive copers were found in both groups, while the shift towards Blunting in the oncology group was accentuated. Within the oncology group, a positive relationship between Blunting scores and time elapsed since diagnosis was observed, suggesting that the increased Blunting in children with cancer is a reactive phenomenon, at least partly a response to the contingencies of cancer and its' treatment. These findings may provide an alternative interpretation to previous reports of increased defensiveness and repression in children with cancer.

Adaptation, Psychological↗
PubMed1995

Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.

PURPOSE: We evaluated cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL). CNS therapy consisted of cranial irradiation (CRT) or no radiation. Children were also randomized to single intravenous high-dose methotrexate (HD-MTX) or conventional-dose methotrexate (CD-MTX) during induction, and all patients received intrathecal (IT) and systemic continuation chemotherapy. PATIENTS AND METHODS: Sixty-six patients treated for ALL on Dana-Farber Cancer Institute protocol 87-01 were evaluated by standardized cognitive and achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, respectively. All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m2) or HD-MTX (4 g/m2) with leucovorin rescue. RESULTS: There was no difference in cognitive outcomes between radiated and unirradiated patients (P > .4). However, the HD-MTX/CRT combination was associated with decreased intelligence quotient (IQ estimate, 9.3 points) for girls only (P < .08). A specific deficit in verbal coding and memory was documented for all patients (P < .0001). CONCLUSION: We conclude the following: (1) 18 Gy CRT per se was not an independent toxic agent for cognitive outcome; (2) HD-MTX during induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding was a consistent finding that was independent of CRT, which implicates some component of chemotherapy, possibly prednisone, as a CNS toxin.

Analysis of Variance↗
PubMed1995

Prognostic factors for prolonged progression-free survival with high-dose chemotherapy with autologous stem-cell support for advanced breast cancer.

PURPOSE: With a median observation time of 50 months from transplant, 13 (22%) of 62 women with metastatic breast cancer treated with high-dose chemotherapy at the Dana-Farber Cancer Institute (DFCI)/Beth Israel Hospital (BIH) remain progression-free. This study determined factors prognostic for prolonged progression-free survival (PFS). METHODS: From June 1988 to January 1992, women who responded to standard chemotherapy received high-dose cyclophosphamide, thiotepa, and carboplatin with autotransplantation. Data encompassing initial breast cancer diagnosis, metastatic presentation, and response to induction treatment were examined for correlations with improved PFS. RESULTS: The 5-year PFS rate for the entire group is estimated to be 21% (95% confidence interval [CI], 10% to 32%). For those patients who attained a complete response (CR) to induction therapy, the 5-year PFS rate is estimated to be 31% (95% CI, 0% to 63%). In univariate analyses, a single metastatic site, CR to induction therapy, prolonged interval from primary diagnosis to first metastases, estrogen receptor (ER)-negative tumors, and older age (> or = 40 years) were associated with prolonged PFS. In multivariate analyses, single metastatic site (P = .002) and attainment of a CR to induction chemotherapy (P = .04) were the most significant predictors for PFS, with a strong trend observed for an interval from primary diagnosis to onset of metastatic disease of 24+ months (P = .066). CONCLUSION: We and others have shown that 10% to 25% of women with metastatic breast cancer are progression-free after high-dose chemotherapy with autotransplantation. Those with chemosensitive disease, minimal tumor bulk, and a prolonged disease-free interval appear to benefit most. Emphasis should continue to focus on the development of more effective cytotoxic regimens and biologic approaches to increase the percentage of patients who may benefit from this approach.

Adolescent↗
PubMed1995

Children's distress during magnetic resonance imaging procedures.

We investigated the epidemiology of pediatric anxiety and distress associated with magnetic resonance imaging procedures (MRIPs). Scores on the State-Trait Anxiety Inventory (Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983) and the State-Trait Anxiety Inventory for Children (Spielberger, Edwards, Lushene, Montuori, & Platzek, 1973), and subjective ratings of distress associated with MRIP were obtained from 55 pediatric oncology patients and their parents. Approximately 30% of children and their parents reported that MRIP produced significant distress. However, parents' ratings of their child's distress were significantly higher than children's self-ratings, and agreement between child and parent pairs was poor. Insertion of an intravenous line was identified as the most aversive component of MRIP by both parents (55%) and children (38%). The selective application of cognitive-behavioral interventions for noninvasive diagnostic procedures is suggested.

Adolescent↗
PubMed1994

Measuring pain in pediatric oncology ICU patients.

Thirty patients (ages 5 to 13) hospitalized in a pediatric oncology intensive care unit (ICU) rated the presence and severity of their pain on the Faces Pain Scale (FPS) and the Poker Chip Tool (PCT). Parents independently rated the child's pain on these scales and each patient's nurse completed the Objective Pain Scale (OPS). Patients' ratings on the FPS correlated significantly with parents' ratings on this scale (tau = .48, P = .002) but not on the PCT (tau = .23, P = .16). Nurses' ratings on the OPS were moderately correlated with patients' FPS ratings (tau = .37, P = .02) but were only weakly associated with PCT ratings (tau = .27, P = .09). The majority of patients, parents, and nurses expressed a preference for the FPS over the PCT. The FPS appears to be a clinically useful and accurate approach for measuring the pain of pediatric oncology patients in an ICU but is limited to those who can participate in a self-report measurement.

Adolescent↗
PubMed1994

Patient characteristics associated with high-risk methotrexate concentrations and toxicity.

PURPOSE: Following high-dose methotrexate (HD-MTX) treatment, delayed MTX elimination is an important problem because it necessitates increased leucovorin rescue and additional hospitalization for hydration and urinary alkalinization. Our purpose was to identify factors associated with high-risk MTX plasma concentrations (defined by plasma concentration > or = 1.0 mumol/L at 42 hours from the start of MTX) and with toxicity. PATIENTS AND METHODS: Variables associated with MTX concentrations and toxicity were assessed in 134 children treated with one to five courses of HD-MTX (900 to 3,700 mg/m2 intravenously [i.v.] over 24 hours for a total of 481 courses) for acute lymphoblastic leukemia (ALL). RESULTS: High-risk MTX concentrations, toxicity (usually mild mucositis), and delay in resuming continuation chemotherapy occurred in 106 (22%), 123 (26%), and 66 (14%) of 481 courses, respectively. Using a mixed effects model for repeated measures, high-risk MTX concentrations were significantly associated with a higher MTX area-under-the-concentration-time curve (AUC), low urine pH, emesis, low MTX clearance, low urine output relative to intake, use of antiemetics during the MTX infusion, and concurrent intrathecal therapy (all p values < .01). Clinical toxicities and delay in resumption of continuation chemotherapy due to myelosuppression were more common in those with high 42-hour MTX concentrations, despite increased leucovorin rescue for all patients with high-risk MTX concentrations. However, with individualized rescue, no patient developed life-threatening toxicity. A more aggressive hydration and alkalinization regimen for subsequent courses reduced the frequency of high-risk MTX concentrations to 7% of courses (13 of 183) (P = .0001), and the frequency of toxicity decreased to 11% of courses (P = .0074). CONCLUSION: This study identified several clinical variables that influence MTX disposition that, when modified, can reduce the frequency of high-risk MTX concentrations and toxicity.

Child↗
PubMed1993

Bilateral Wilms tumor. Review of outcome, associated abnormalities, and late effects in 36 pediatric patients treated at a single institution.

BACKGROUND: Patients with bilateral Wilms tumor have an increased incidence of associated abnormalities and nephrogenic rests and require individualized multimodality therapy for cure. The authors reported the associated abnormalities, outcome, complications, and late effects of treatment in a group of children with bilateral Wilms tumor treated at St. Jude Children's Research Hospital, Memphis, Tennessee, over a 28-year period. METHODS: The records of 36 consecutive pediatric patients diagnosed with bilateral Wilms tumor between 1962-1990 were analyzed. Biopsy material was also reviewed, with particular emphasis on characterization of nephrogenic rests and histology. RESULTS: Twenty-nine patients had synchronous tumors and 7 had metachronous lesions. Associated physical abnormalities were present in 12 patients and involved the genitourinary, cardiovascular, integumentary, and musculoskeletal systems. The overall survival for patients with metachronous tumors (71%) was similar to that for those with synchronous tumors (70%). There was no effect of age or the presence of nephroblastomatosis. Two patients with synchronous tumors initially treated with nephrectomy eventually required bilateral nephrectomies for contralateral recurrence after chemotherapy and radiation therapy. Nephrogenic rests were present in 22 of 30 evaluable patients. Two of three patients with metachronous tumors had intralobar nephrogenic rests. Bilateral renal salvage procedures were demonstrated to be technically feasible and effective in controlling disease without compromising renal function or survival. Late effects included scoliosis in three patients treated before 1970, cardiomyopathy in one patient who received 300 mg/m2 doxorubicin and 12 Gy pulmonary irradiation, and benign tumors in two patients, one of whom also had a bowel obstruction. Serum creatinine, urea nitrogen, and blood pressure were normal in 23 of 26 survivors. CONCLUSIONS: The authors' experience supports a favorable outcome with minimal late effects for patients with bilateral Wilms tumor who receive individualized therapy at pediatric oncology centers.

Child↗
PubMed1993

Chlorpromazine with and without lorazepam as antiemetic therapy in children receiving uniform chemotherapy.

We prospectively studied the efficacy and adverse effects of chlorpromazine (30 mg/m2 given intravenously) plus lorazepam (0.04 mg/kg given intravenously) versus chlorpromazine alone in a controlled, double-blind, randomized, parallel-design investigation in 25 children (1.5 to 17.3 years of age) with acute lymphoblastic leukemia. Response to other antiemetics in eight children refusing random assignment to treatment was also evaluated. All children were receiving intravenous infusions of teniposide plus cytarabine, the pharmacokinetics of which were characterized for each of the one to four courses. There were no differences between the 11 patients randomly assigned to receive chlorpromazine alone and the 14 randomly assigned to receive lorazepam plus chlorpromazine in the number of emesis episodes (6.0 vs 5.9; p = 0.53), frequency of dystonic reactions (3% vs 5%), or akathisia (13 vs 10%). The only serious adverse event, symptomatic hypotension, occurred in a boy receiving chlorpromazine plus lorazepam. An exploratory pharmacodynamic analysis revealed that the only variable that correlated with vomiting was cytarabine 1 1/2-hour plasma concentration (p = 0.007). Children who received either chlorpromazine plus lorazepam or chlorpromazine alone had fewer episodes of vomiting than those who received "conventional" antiemetic therapy (6.0 vs 8.6; p = 0.01). We conclude that the severity of emesis is related to the plasma concentration of cytarabine; that intravenously administered chlorpromazine is as effective as chlorpromazine plus lorazepam in preventing chemotherapy-induced vomiting; and that the potential for adverse effects with the addition of lorazepam may be a disadvantage.

Adolescent↗
PubMed1993

Reversal of dopamine-refractory septic shock by diethyldithiocarbamate, an inhibitor of endothelium-derived relaxing factor.

Septic shock occurs when endotoxin and other bacterial substances induce the release of host products that act in concert to alter the circulation. Recently, investigators have speculated that endothelium-derived relaxing factor (EDRF), a potent endotoxin-inducible vasodilator, plays an important role in the pathogenesis of septic shock. Diethyldithiocarbamate (DTC), a copper chelator lacking intrinsic vasoactivity, inactivates EDRF. Intravenous DTC was compared with placebo and dopamine in 12 matched sets of 3 rabbits with induced Escherichia coli sepsis. Median levels of bacteremia and endotoxemia were similar in the 3 treatment groups. DTC-treated animals had higher mean arterial pressure and lower heart rates and blood lactate concentrations than either placebo- or dopamine-treated animals (P = .013, P < .001, and P = .001, respectively). These effects were independent of plasma catecholamine concentrations. DTC can reverse septic shock that is refractory to conventional therapy, and these results suggest that EDRF is an important mediator of septic shock.

Animals↗
PubMed1993

Factors associated with social and behavioral problems among children recently diagnosed with brain tumor.

Compared the psychological adjustment of 81 children with brain tumors to that of 31 control children with various malignancies not involving the central nervous system. Both groups exhibited significantly increased frequencies of elevations on one or more age- and gender-corrected Social Competence and Behavior Problems scales of the Child Behavior Checklist (CBCL) relative to normative expectations. Comparison of the Brain Tumor and Cancer Control groups revealed no significant differences on any CBCL scale. Among children diagnosed with brain tumors, stepwise multiple regression analyses revealed that low child IQ, residence in a single-parent family, moderate to severe disfigurement, low SES, tumor location, and severe functional impairment were associated with decreased Social Competence scores. Elevated Behavior Problems scores were associated with younger maternal age at the child's birth, tumor location, and residence in a single-parent family. Results reinforce the need to consider complex relationships between demographic characteristics of the child's family, type of brain damage, and the cosmetic and functional status of the child in determining acute psychological adjustment of brain-damaged children.

Adaptation, Psychological↗
PubMed1993

Efficacy and toxicity of multiagent chemotherapy and low-dose involved-field radiotherapy in children and adolescents with Hodgkin's disease.

PURPOSE: Between May 1980 and September 1990, 85 patients with Hodgkin's disease were treated with a regimen designed to increase cure rates while reducing late toxicity. PATIENTS AND METHODS: Therapy consisted of five cycles of cyclophosphamide, Oncovin (vincristine; Eli Lilly and Co, Indianapolis, IN), and procarbazine (COP), alternated with four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and low-dose (20 Gy) regional radiotherapy. Vincristine and cyclophosphamide were administered as tolerated during irradiation and during the 2- to 4-week rest period between radiation volumes. The need for staging laparotomy was defined by clinical presentation. RESULTS: The median age at diagnosis was 14 years (range, 4 to 20), and 56% of patients were male. The majority (67%) had stage III or IV disease and 68% (19 of 28) of stage II patients had bulky mediastinal disease. Nodular sclerosing histology predominated (67%). Ninety-three percent of patients were alive without disease with a median follow-up of 4.1 years. Abnormalities were detected on chest roentgenograms and/or pulmonary function tests in 58% and 25% of clinically asymptomatic patients who were tested at least 1 year after completion of therapy. The only symptomatic patient had pulmonary fibrosis after treatment with bleomycin (20 U/m2) and mantle (20 Gy)/lung (13 Gy) irradiation, and developed multiple spontaneous pneumothoraces that required cortical stripping. One patient had congestive heart failure 19 months post-treatment, and two had abnormalities on echocardiograms. Thyroid abnormalities occurred in 21 (27%) patients who were assessable for late toxicity. The majority of female patients have had regular menstrual cycles. Six developed ovarian failure, and 10 have had a total of 17 pregnancies. Other than one documented case of oligospermia, information was not available on male fertility. CONCLUSION: The results demonstrate excellent disease control for the COP/ABVD regimen, with acceptable toxicity.

Adolescent↗
PubMed1993

Acute megakaryoblastic leukemia in children and adolescents: a retrospective analysis of 24 cases.

In order to characterize the clinical, cytogenetic, and outcome features of childhood acute megakaryoblastic leukemia (AMKL), we reviewed 24 cases; 14 were identified among 150 consecutive newly diagnosed acute myelogenous leukemia (AML) patients at St. Jude Children's Research Hospital, and 10 were cases referred to the National Institute of Cancer in Rio de Janeiro, Brazil. There were 5 Down syndrome patients and one patient with chronic myeloid leukemia (Ph+) in blastic crisis. Twelve patients had significant hepatosplenomegaly. Leukemic cell morphology and cytochemistry were consistent with the M7 classification in 17 cases, and all cases tested expressed megakaryocytic surface antigens. AMKL patients were significantly younger than other AML patients (P = 0.0001) and had poorer responses to therapy (P = 0.03, univariate analysis only). Ten of 24 failed induction, and only 5 are disease-free at 6 months to 4.5+ years. We conclude that AMKL usually affects young children, frequently producing marked organomegaly. It comprises approximately 10% of pediatric AML cases, and responds poorly to intensive AML therapies.

Adolescent↗
PubMed1993

Chest tube stripping in pediatric oncology patients: an experimental study.

BACKGROUND: Stripping of chest tubes to promote drainage of the thorax of postthoracotomy patients has been routine practice, based on tradition. Recent published findings indicate that significant negative pressures are generated in the tube during stripping that could cause pain, bleeding and possible damage to the patient's lung tissue. OBJECTIVE: To determine whether pediatric oncology patients whose chest tubes were not stripped would differ in frequency of pain, fever or lung complications from patients who underwent routine tube stripping. METHODS: Data were collected at multiple points during the first 72-hour postoperative period from 16 patients assigned to the stripped or unstripped groups. Pain was measured by the Faces Pain Scale and the Visual Analogue Scale; temperature, by electronic thermometer; and lung complications, by stethoscope and radiographs. Both groups, which were comparable for age, primary diagnosis and prior history of lung problems, received identical supportive nursing and medical care, with the physicians blind to group assignment. RESULTS: The two groups did not differ significantly in frequency of pain, incidence of fever, breath sounds or radiographic findings across measurement points. A strong correlation was found between the pain scores using the two instruments. DISCUSSION: Patients whose tubes were not stripped did not have an increased risk of infection or lung complications. Study findings indicated that stripping did not increase the frequency of pain. CONCLUSIONS: Stripping of chest tubes as a routine postoperative measure is questioned.

Adolescent↗
PubMed1993

Chemotherapy induced nausea and emesis in pediatric cancer patients: external validity of child and parent emesis ratings.

Children's and parent's subjective ratings of the frequency and severity of nausea and emesis were assessed among 33 children with acute lymphoblastic leukemia receiving identical chemotherapy. Parents were trained to record the frequency of the child's actual emesis episodes during chemotherapy. Although parent and child ratings of nausea were significantly correlated, children generally rated their nausea and emesis as more frequent and more severe than did their parents. Parent ratings showed inadequate external validity when compared with behavioral observations. Children with greater anxiety and higher subjective ratings subsequently exhibited more frequent episodes of emesis by observation, suggesting that their perceptions of symptoms based on previous chemotherapy experiences may predict emesis during different chemotherapy. In a stepwise multiple regression analysis, antiemetic regimen and the child's anxiety as rated by the parent combined to account for approximately 47% of the variance in number of episodes of emesis. These findings are discussed in the context of factors limiting validity of parent and child reports of children's symptomatology with implications for future epidemiologic and intervention research.

Adolescent↗
PubMed1992

Neuropsychological status of children treated for brain tumors: a critical review and integrative analysis.

The literature on the neuropsychological status of children with primary brain tumors was reviewed to identify English-language publications reporting the results of standardized, quantitative measures of patient function. The 22 studies that met these review criteria, representing 544 patients, were evaluated to assess the relationship between traditional risk factors (age at diagnosis, tumor location, radiation therapy, and time since completion of treatment), as well as subsequent intellectual development, academic achievement, psychosocial adjustment, and neuropsychological status. The impact of other potentially salient factors, such as seizures and sensory and motor deficits, was evaluated when possible. Despite inconsistent reporting of demographic and treatment-related effects across studies which precluded formal meta-analysis, we were able to confirm the primary importance of radiation therapy volume and age at treatment on IQ. No effects were detected for tumor location. Younger children treated with cranial (whole brain) irradiation showed a 14-point deficit in IQ as compared with their older counterparts. No significant differences were noted between older children receiving local or cranial irradiation, although both groups had IQ levels 12-14 points lower than those not irradiated. The high-risk groups identified in this study require increased clinical surveillance. Definitive evaluation of potential risk factors for neuropsychological impairment will depend on more complete reporting of relevant patient characteristics and interinstitutional studies.

Adolescent↗