PubMed Health⌕ Search

Biomedical subjects

M M Hudson

Publications and source records attributed to M M Hudson.

At least 19 recordsLinked to original sources
PubMed2001

Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer.

PURPOSE: To test if methylphenidate (MPH) has an objective beneficial effect on immediate performance on tests of neurocognitive functions among learning-impaired survivors of childhood acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT). PATIENTS AND METHODS: From July 1, 1997 through December 31, 1998, 104 long-term survivors of childhood ALL or a malignant BT completed neurocognitive screening for learning impairments and concurrent problems with sustained attention. Eligibility criteria for the MPH trial included an estimated intelligence quotient greater than 50, academic achievement in the 16(th) percentile or lower for age in reading, math, or spelling, and an ability to sustain attention on a computerized version of the Conners' Continuous Performance Test (CPT) in the 16(th) percentile or lower for age and sex. Of the 104, 32 (BT, n = 25; ALL, n = 7) were eligible on the basis of these a priori criteria for a randomized, double-blinded, placebo-controlled trial of MPH. The patients ingested a placebo (lactose) or MPH (0.6 mg/kg; 20 mg maximum) and repeated selected portions of the screening battery 90 minutes later. RESULTS: Compared to the 17 patients randomized to the placebo group, the 15 patients randomized to the MPH group had a significantly greater improvement on the CPT for sustained attention (errors of omission, P =.015) and overall index (P =.008) but not for errors of commission (indicative of impulsiveness) nor reaction times. A trend for greater improvement in the MPH group on a measure of verbal memory failed to reach statistical significance. No trend was observed for MPH effectiveness in improving learning of a word association task. No significant side effects from MPH were observed. CONCLUSION: MPH resulted in a statistically significant improvement on measures of attention abilities that cannot be explained by placebo or practice effects.

Administration, Oral↗
PubMed2001

Bone mineral decrements in survivors of childhood acute lymphoblastic leukemia: frequency of occurrence and risk factors for their development.

We assessed the clinical and treatment factors that predispose survivors of childhood acute lymphoblastic leukemia (ALL) to low bone mineral density (BMD). Using quantitative computed tomography, we determined the frequency of low BMD (defined as >1.645 standard deviations (SD) below the mean) in leukemia survivors treated with multiagent chemotherapy including prednisone and antimetabolite. All participants had completed therapy at least 4 years earlier, remained in continuous complete remission, and had no second malignancies. We statistically correlated BMD results with patient characteristics and treatment histories. Among 141 survivors (median age, 15.9 years; median time after diagnosis, 11.5 years), median BMD z score was -0.78 SD (range, -3.23 to 3.61 SDs). Thirty participants (21%; 95% confidence interval, 15% to 29%) had abnormally low BMD, a proportion significantly (P < 0.0001) greater than the expected 5% in normal populations. Risk factors for BMD decrements included male sex (P = 0.038), Caucasian race (P < 0.0001), and cranial irradiation (P= 0.0087). BMD inversely correlated with cranial irradiation dose. BMD z scores of patients who received higher doses of antimetabolites were lower than those of other patients. Childhood ALL survivors are at risk to have low BMD, especially males, Caucasians, and those who received cranial irradiation.

Adolescent↗
PubMed2000

Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.

Administration, Oral↗
PubMed2000

Late effects of treatment in survivors of childhood acute myeloid leukemia.

PURPOSE: To investigate the incidence of and risk factors for late sequelae of treatment in patients who survived for more than 10 years after the diagnosis of childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: Of 77 survivors (median follow-up duration, 16. 7 years), 44 (group A) had received chemotherapy, 18 (group B) had received chemotherapy and cranial irradiation, and 15 (group C) had received chemotherapy, total-body irradiation, and allogeneic bone marrow transplantation. Late complications, tobacco use, and health insurance status were assessed. RESULTS: Growth abnormalities were found in 51% of survivors, neurocognitive abnormalities in 30%, transfusion-acquired hepatitis in 28%, endocrine abnormalities in 16%, cataracts in 12%, and cardiac abnormalities in 8%. Younger age at the time of diagnosis or initiation of radiation therapy, higher dose of radiation, and treatment in groups B and C were risk factors for the development of academic difficulties and greater decrease in height Z: score. In addition, treatment in group C was a risk factor for a greater decrease in weight Z: score and the development of growth-hormone deficiency, hypothyroidism, hypogonadism, infertility, and cataracts. The estimated cumulative risk of a second malignancy at 20 years after diagnosis was 1.8% (95% confidence interval, 0.3% to 11.8%). Twenty-two patients (29%) were smokers, and 11 (14%) had no medical insurance at the time of last follow-up. CONCLUSION: Late sequelae are common in long-term survivors of childhood AML. Our findings should be useful in defining areas for surveillance of and intervention for late sequelae and in assessing the risk of individual late effects on the basis of age and history of treatment.

Acute Disease↗
PubMed2000

Hepatitis C infection among survivors of childhood cancer.

Preliminary reports have suggested that survivors of childhood cancer and aplastic anemia who are infected with the hepatitis C virus (HCV) have a low risk for progression to significant liver disease. Among our surviving patients who were transfused between 1961 and March 1992, 77 (6.6% of surviving patients tested thus far) have evidence of HCV infection, whereas 4 surviving patients who were transfused after March 1992 are HCV-infected. One patient chronically infected with HCV died of liver failure, and 2 patients died of hepatocellular carcinoma. To characterize the risk for these and other complications, 65 patients are enrolled in a longitudinal study of HCV infection, of whom 58 (89.2%) had circulating HCV RNA at the time of protocol enrollment, with genotypes 1A and 1B most commonly isolated. Most enrolled patients have few or no symptoms, carry out normal activities, and have normal liver function. To date, 35 patients have undergone liver biopsy for abnormal liver function since the diagnosis of primary malignancy; central pathology review shows 28 (80%) have chronic active hepatitis, 25 (71%) have fibrosis, and 3 (9%) have cirrhosis. These preliminary data suggest that though most survivors of childhood cancer who are infected with HCV are clinically well, some are at risk for clinically significant liver disease. Identification of other HCV-infected patients and prospective monitoring of this cohort are ongoing to determine the risk for, and to identify factors associated with the progression of, liver disease.

Adult↗
PubMed1999

Long-term follow-up of patients treated with primary radiotherapy for supradiaphragmatic Hodgkin's disease at St. Jude Children's Research Hospital.

OBJECTIVE: To assess disease control, patterns of relapse, factors predictive of relapse, and late effects of treatment, we reviewed all cases of supradiaphragmatic (SD) Hodgkin's disease (HD) treated with primary radiation therapy (RT) at our institution. METHODS: We retrospectively reviewed the disease characteristics, treatment history, and long-term outcome of the 106 patients with Stage I and II supradiaphragmatic HD who received definitive irradiation at St. Jude Children's Research Hospital between 1970 and 1995. As of the date of analysis, 95 patients are alive, with a median follow-up of 13.3 years (range, 1.9-24.2 years). RESULTS: The median age at diagnosis was 14.7 years (range, 3.7-22.7). Involved-field RT was given to 13 patients (12%), whereas 37 (35%) had mantle RT, 51 patients (48%) had subtotal nodal irradiation, and 5 (5%) had total nodal irradiation. Relapsed disease developed in 26 patients at a median of 1.8 years (range, 0.2-9.3 years). The 5- and 10-year estimated cumulative incidences of relapse were 20.9% +/- 4.0% and 25.1% +/- 4.3%, respectively. With a median dose of 36 Gy (range, 32-40), in-field failure rate was 6.2%, whereas subdiaphragmatic relapse in sites irradiated prophylactically was 1.5%. There was a trend toward an increased incidence of relapse with higher ESR (p = 0.088) and greater number of sites of disease (p = 0.087). Age, stage, histology, nodal disease > or = 6 cm, the presence of bulky mediastinal disease, and the method of staging did not affect the incidence of relapse. The pattern of failure could not be predicted based on the stage of disease, the extent of subdiaphragmatic staging, the extent of radiation therapy, or the sequence of RT fields-"ping pong" vs. sequential. Subset analysis of Stage II patients revealed significantly more relapses in clinically staged patients. Excluding Stage IA patients with high cervical disease or peripheral nodal disease, nodal extension failures were more common for patients undergoing limited-volume RT, whereas extranodal relapses were likely after STNI or TNI. The estimated 10- and 15-year cumulative incidences of second malignancies were 2.9% +/- 1.6% and 7.9% +/- 3.3%, respectively. Our patients are at increased risk of second malignancies (11-fold), and fatal cardiac (68-fold) and infectious (33-fold) complications. Overall survival at 10 years was 90.8% +/- 3.2%; event-free survival was 72.1% +/- 5.0%. CONCLUSIONS: The current analysis confirms the curative potential of RT for HD in children and adolescents. Despite successful salvage therapy, relapsed disease remained the principal cause of death in our cohort. Excess risk of septic death in asplenic patients, fatal heart disease, and second malignancies may further compromise the ultimate cure of HD in long-term survivors.

Adolescent↗
PubMed1999

Feasibility of implementing health promotion interventions to improve health-related quality of life.

Survivors of childhood cancer are a growing and vulnerable population. Cure rates for pediatric cancers now exceed 60% and, by the year 2000, an estimated 1 of every 1,000 young adults will be a cancer survivor. Because this population is at increased risk for late medical and neoplastic complications that impact adversely on health-related quality of life, it is important to investigate methods to promote risk reduction by motivating survivors to practice health-promoting behaviors. With this background, we initiated a prospective, randomized, controlled feasibility study in which survivors attending a long-term follow-up clinic were randomized to receive standard care or standard care plus an educational intervention. Our objectives were to determine if the intervention would improve the survivors' knowledge about their cancer treatment and risks of late effects and increase their practice of health-protective behaviors. Since July 1995, 272 of 318 families (86%) approached about the study agreed to participate. Of these, 266 are evaluable for assessment of baseline knowledge and health behaviors. Demographic features, baseline knowledge, health perceptions and health behaviors did not differ among randomized groups. Assessment of the intervention's efficacy at changing health behaviors of survivors randomized to the intervention group will be available when the 1-year follow-up evaluations are completed for the study cohort. Our preliminary experience with this pilot study supports the feasibility of educational intervention research in a specialty clinic dedicated to monitoring long-term childhood cancer survivors. Int. J. Cancer Suppl. 12:138-142, 1999.

Adolescent↗
PubMed1999

Health status and health-related quality of life in long-term adult survivors of pediatric solid tumors.

We have examined the influence of selected factors (gender, marital status, socio-economic status, co-morbid conditions, access to medical care, age at diagnosis, intensity of therapy and time since diagnosis) on subsequent health status and health-related quality of life (HRQL) of long-term survivors of pediatric solid tumors. Two hundred and twenty individuals who had survived a pediatric solid tumor 15 years or longer completed telephone and written assessments of their current status. Health status was assessed using the Late Effects of Normal Tissues toxicity scale. HRQL was investigated using the Ferrans and Powers Quality of Life Index-Cancer (QLIC) and the EORTC Quality of Life Questionnaire C30 (QLQ-C30). Results indicated that health status and HRQL were better in survivors treated with low-intensity therapy. One hundred and thirty respondents (59.1%) reported at least 1 serious toxicity. Dyspnea and fatigue were commonly reported in survivors of Hodgkin's disease. Correlational analyses showed that predictors of health status included socio-economic status, marital status and the presence of co-morbid factors. Mean HRQL scores for the 4 domains of the Ferrans and Powers QLIC and the functional scales of the EORTC QLQ-C30 indicated that most of the survivors were experiencing moderately good to excellent HRQL. One-third of survivors reported that their history of cancer had an adverse impact on their current financial status. Prediction models constructed for 3 of the domains from the 2 HRQL instruments are presented (health and functioning, global HRQL and financial impact). Within these 3 models, consistent predictors of HRQL outcomes included health status, presence of dyspnea or pain, marital status and socio-economic status.

Adult↗
PubMed1999

Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist.

OBJECTIVE: Hypothalamic obesity is a rare sequela of cranial insult, for which pathogenesis and treatment remain obscure. In rodents ventromedial hypothalamic damage causes hyperphagia, obesity, hyperinsulinism, and insulin resistance. Reduction of insulin secretion in humans may attenuate weight gain. METHODS: Eight children with intractable obesity after therapy for leukemia or brain tumors underwent oral glucose tolerance testing (OGTT) with simultaneous insulin levels before and after treatment with octreotide for 6 months. RESULTS: In comparison with a 6-month pre-study observation period, patients exhibited weight loss (+6.0 +/- 0.7 kg vs -4.8 +/- 1.8 kg; P =.04) and decrease in body mass index (+2.1 +/- 0.3 kg/m(2) vs -2.0 +/- 0.7 kg/m(2); P =.0001). Recall calorie count decreased during the 6 months of treatment (P =. 015). OGTT demonstrated biochemical glucose intolerance in 5 of 8 patients initially and in 2 of 7 at study end, whereas insulin response was decreased (281 +/- 47 microU/mL vs 114 +/- 35 microU/mL; P =.04). Percent weight change correlated with changes in insulin response (r = 0.72, P =.012) and changes in plasma leptin r = 0.76, P =.0004). CONCLUSIONS: Patients with hypothalamic obesity demonstrate excessive insulin secretion. Octreotide administration promoted weight loss, which correlated with reduction in insulin secretion on OGTT and with reduction in leptin levels. Pre-study biochemical glucose tolerance improved in several patients while they were receiving octreotide. These results suggest that normalization of insulin secretion may be an effective therapeutic strategy in this syndrome.

Adolescent↗
PubMed1999

Diagnosis of hidden central hypothyroidism in survivors of childhood cancer.

To determine how often central hypothyroidism remains undetected by routine out-patient tests of thyroid hormone, we studied 208 pediatric cancer survivors referred for evaluation because of signs of subtle hypothyroidism or hypopituitarism. Of the 208 (68 females and 140 males), 110 had brain tumors, 14 had other head/neck tumors, 11 had solid tumors remote from head and neck, and 73 had leukemia. Patients were evaluated 1-16 yr (mean, 6.1+/-4.1 yr) after tumor diagnosis. The nocturnal TSH surge and response to TRH were measured. Of 160 patients with free T4 in lowest third of normal, 34% had central hypothyroidism (blunted TSH surge or low/delayed TSH peak or delayed TSH decline after TRH); 9% had central hypothyroidism with mild TSH elevation (mixed hypothyroidism). Another 16% had mild primary hypothyroidism (TSH, 5-15 mU/L). Of 48 with free T4 in the upper two thirds of normal, 14% had central hypothyroidism; 17% had mild primary hypothyroidism. Incidence of central, mixed, and mild primary hypothyroidism 10 yr after tumor diagnosis was significantly related to total cranial radiation dose (P < 0.0001). Of 62 patients with central hypothyroidism, 34% had not developed GH deficiency. TSH surge identified 71%, and response to TRH identified 60% of those with central hypothyroidism. More than half of the slowly growing patients who have received cranial or craniospinal radiation for childhood cancer develop subtle hypothyroidism. In our study group, 92% of patients with central hypothyroidism and 27% with mixed hypothyroidism would have remained undiagnosed using baseline thyroid function tests alone. Both TSH surge and response to TRH must be evaluated to identify all of these patients.

Adolescent↗
PubMed1999

Treatment of pediatric Hodgkin's lymphoma.

Today the majority of children and adolescents diagnosed with Hodgkin's lymphoma will enjoy long-term disease-free survival. As a result, contemporary treatment strategies have focused on reducing therapy for patients with favorable disease presentations and reserved aggressive treatment modalities for patients with relapsed or refractory disease. The desire to avoid late treatment toxicity has prompted refinements in therapy designed to reduce growth impairment, second malignancy, and life-threatening organ dysfunction in long-term survivors. Treatment with radiation therapy alone is recommended only for older patients with localized disease who have achieved skeletal maturity, but requires surgical staging and places greater volumes of normal tissues at risk for late carcinogenesis. Treatment with chemotherapy alone avoids the long-term growth, organ dysfunction, and solid tumor induction associated with high-dose, extended-field radiation. However, these protocols prescribe higher cumulative doses of alkylating agent chemotherapy, which may increase the risk of treatment complications from myelosuppression, gonadal injury, and secondary leukemia. Combined modality therapy regimens have resulted in excellent treatment outcomes and reduced the incidence of treatment sequelae by utilizing lower doses and smaller volumes of radiation therapy and fewer cycles of less toxic chemotherapy in clinically staged children. Risk-adapted therapies using two to four cycles of multiagent chemotherapy and lower radiation doses and volumes have maintained excellent disease-free survival rates in clinically staged patients with localized favorable disease presentations. Novel approaches including compacted dose-intensive multiagent chemotherapy are currently under investigation with the objectives of improving outcome and reducing treatment sequelae in patients with advanced and unfavorable disease.

Adolescent↗
PubMed1998

Breast masses in women treated for childhood cancer: incidence and screening guidelines.

BACKGROUND: The authors' aims were to define the frequency, characteristics, and methods of detection of breast masses in young women treated for childhood cancer and to develop screening guidelines for the growing population of long term survivors. METHODS: The authors reviewed medical records of all female patients treated for malignancy at a childhood cancer center over a 34-year period to identify those who developed a breast mass and to determine the cumulative incidence of breast cancer as a second primary cancer. RESULTS: A breast mass was identified in 66 patients who had been diagnosed with a malignancy at a median age of 13.8 years (range, 0.4-24.4 years). Masses were initially detected by breast self-detection in 32 and clinical examination in 28; the method of detection was unknown in 6 cases. Breast lesions were benign in 41 patients and malignant in 26; 1 patient had both a benign and a malignant lesion. Of the 26 malignant masses, 14 represented metastases of the primary malignancy and 12 were primary breast cancers as second primary cancers. The median interval to a primary breast cancer as a second primary cancer was 13.6 years (range, 9.2-24.4 years), and the median age at detection was 27.7 years (range, 12.5-43.1 years). The 25-year cumulative incidence of primary breast cancer as a second primary cancer in this cohort was 1.7% (95% CI, 0.4%-2.9%). This represented a 20-fold increase (95% CI, 10-36) over the expected incidence in age-matched and race-matched controls. CONCLUSIONS: Young women treated for childhood cancer have a significantly increased risk of breast cancer compared with age-matched controls. For this group of patients, the authors recommend patient education regarding this risk and the importance of properly conducted self-examination as the foundation of breast cancer screening. In addition, clinical and mammographic screening should be instituted at a younger age and performed more frequently than recommended for the general population of women.

Adolescent↗
PubMed1998

Profound abnormality of the B/T lymphocyte ratio during chemotherapy for pediatric acute lymphoblastic leukemia.

The fluorescence-activated cell sorter (FACS) was utilized to phenotype lymphocyte compartments in children receiving intensive chemotherapy for acute lymphoblastic leukemia (ALL). Sixteen patients (eight males and eight females) of diverse ages, risks of relapse, and within weeks 7-53 of maintenance/continuation chemotherapy treatment were arbitrarily selected for study. All 16 patients had profound B cell lymphopenia. In contrast, T cell numbers were often normal or marginally low, and accounted for up to 98% of the lymphocyte populations. No abnormality in T cell phenotypes could be demonstrated. Due to the highly skewed B/T lymphocyte ratios in these ALL patients, the absolute white blood cell counts and lymphocyte percentages were not predictive of the underlying B cell lymphopenia. Patients were also tested for serum immunoglobulin levels and most had abnormally low IgG and IgM. None of four patients immunized with the 1996-1997 influenza virus vaccine seroconverted to at least two vaccine antigens as compared to 10 of 10 healthy, age-matched controls. In total, these data highlight for the first time the profound abnormality of the B/T lymphocyte ratio in patients during treatment for ALL, and argue for consideration of B cell-targeted immunotherapy.

Adolescent↗