Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study.

Conditioning regimens for children with ALL have generally included total body irradiation (TBI), which may result in significant sequelae. The primary aim of this study was to evaluate the outcome for children with ALL undergoing allogeneic stem cell transplant (SCT) with either busulfan (Bu) or TBI regimens. Patients <21 years with ALL undergoing allogeneic SCT were eligible. Conditioning included either Bu or TBI, with etoposide 40 mg/kg and cyclophosphamide 120 mg/kg. Randomization was stratified based upon duration of remission, remission status, and prior cranial irradiation. A total of 43 patients were enrolled; 21 received Bu and 22 TBI. Median patient age was 8 years (0.5-20 years). Remission status included 12 patients in CR1, 25 in CR2, and six in CR3. At a median follow-up of 43 months, event-free survival (EFS) is 45% at 3 years, with 29% EFS in the Bu arm and 58% in the TBI arm (P=0.03). There was no significant difference between Bu and TBI for patients who received stem cells from related donors (36 vs 58%, P=0.3). However, for URD, EFS was 20% for Bu and 57% for TBI (P=0.04). Relapses were similar in both arms. This randomized prospective study suggests that Bu is inferior to TBI for pediatric patients with ALL undergoing allogeneic SCT.

Hypofractionated moderate dose radiation, intrathecal chemotherapy, and repetitive reinduction/reconsolidation systemic therapy for central nervous system relapse of acute lymphoblastic leukemia in children.

BACKGROUND: We assessed efficacy and morbidity of chemotherapy and 1, 800 cGy of hypofractionated craniospinal irradiation (CSI) in children with central nervous system (CNS) relapse following first remisssion of acute lymphoblastic leukemia (ALL). PROCEDURE: Nineteen patients with isolated CNS relapse and 4 with combined CNS/marrow or CNS/testicular relapse received treatment according to Children's Hospital of Philadelphia (CHOP) protocols CHP-449 and CHP-497. CNS treatment included intrathecal methotrexate, cytarabine, and hydrocortisone and 1,800 cGy CSI in 16 fractions over 12 months. Systemic therapy consisted of reinductions with vincristine, prednisone, and daunorubicin and reconsolidations with cytarabine, etoposide, and L-asparaginase every 56 days for 2 years. Outcome measures were event-free survival (EFS), survival, growth, and neuropsychologic assessment or school performance. RESULTS: Follow-up of survivors from first relapse ranges from 52 to 133 months(median 91 months). Actuarial survival and EFSat 10 years are 58% (CI95 = 38-78%) and 54% (CI95 = 32-76%). Events include 2 second CNS, 4 marrow, 1 testicular, and 2 testicular/marrow relapses and 1 secondary leukemia. EFS is 100% (CI95 = 93-100%) in 9 patients with recurrence more than 26 months from diagnosis. Three patients have significant treatment-related reduction in stature. Median full-scale IQs of 6 patients tested were 112 pretreatment and 111 posttreatment among surviving patients. All 17 survivors attend regular school, but 2 receive supplementary special services. CONCLUSIONS: Lower dose, hypofractionated CSI, intrathecal chemotherapy, and moderately intensive systemic chemotherapy provide excellent disease control for patients with late isolated CNS or combined marrow and CNS relapse. Children with brief first remissions remain at substantial risk of subsequent relapse with this therapy, especially in the marrow and testes.

Surviving cancer competently intervention program (SCCIP): a cognitive-behavioral and family therapy intervention for adolescent survivors of childhood cancer and their families.

Psychological reactions to having had childhood cancer often continue after treatment ends, for survivors and their parents. Based on our previous research, we developed an intervention program for adolescent survivors of childhood cancer, their parents, and siblings. Surviving Cancer Competently: An Intervention Program--SCCIP--is a one-day family group intervention that combines cognitive-behavioral and family therapy approaches. The goals of SCCIP are to reduce symptoms of distress and to improve family functioning and development. SCCIP is described and data from a pilot study of 19 families are presented. Program evaluation data indicated that all family members found SCCIP helpful. Standardized measures administered before the intervention and again at 6 months after SCCIP showed that symptoms of posttraumatic stress and anxiety decreased. Changes in family functioning were more difficult to discern. Overall, the results were promising with regard to the feasibility of the program and its potential for reducing symptoms of distress for all family members.

Monitoring styles in women at risk for cervical cancer: implications for the framing of health-relevant messages.

We explored the interaction effects of individual attentional style (high versus low monitoring) and the framing of informational messages on the responses of women undergoing diagnostic follow-up (colposcopy) for precancerous cervical lesions. Prior to the colposcopic procedure, patients (N=76) were randomly assigned to one of three preparatory conditions: (a) Loss-framed message, which emphasized the cost of nonadherence to screening recommendations; (b) Gain-framed message, which emphasized the benefit of adherence; and (c) Neutrally-framed message. It was hypothesized that low monitors (who are more positively biased about their health) would show a more adaptive pattern of response to loss-framed information than high monitors (who are more negatively biased about their health). The results of a series of hierarchical multiple regression analyses were consistent with this prediction. Low monitoring was associated with greater knowledge retention (beta=.61, p<.05) and less canceling/rescheduling of follow-up appointments in the loss condition than in the neutral condition (beta=.82, p<.002). High monitoring, however, was associated with greater intrusive ideation when information was presented in the loss-oriented frame as compared to the neutral frame (beta=.99, p<.01). Knowledge retention and screening adherence were not affected by the framing manipulation. The differences between high versus low monitors as a function of loss or neutral frame suggest an interaction effect, wherein both the type of framing message and the individual's attentional style lead to distinctive cognitive-affective and behavioral patterns. The findings may have clinical implications for the tailoring of health messages to the individual's signature style.

Neuropsychological outcome of children undergoing bone marrow transplantation.

The purpose of the study was to prospectively evaluate the neuropsychological functioning of children and adolescents receiving a bone marrow transplant (BMT). One hundred and twenty-two children with malignant or nonmalignant disorders and no previous cranial radiation therapy received a pre-BMT neuropsychological evaluation. Surviving children received a 1 year post-BMT neuropsychological evaluation. Patients were placed in a chemotherapy only (chemo) or a chemotherapy and total body irradiation (chemo + TBI) group for statistical analysis. The data were analyzed by t-tests for paired samples. There were no statistically significant differences. Regression analysis failed to identify treatment, age and gender effects. The results suggest that global and specific areas of neuropsychological functioning 1 year post-BMT were not detrimentally affected by chemotherapy or chemotherapy with total body irradiation.

A framework for understanding and responding to the psychosocial needs of children with Langerhans cell histiocytosis and their families.

This article presents a five-point framework to help health-care providers understand and manage important psychosocial issues related to Langerhans cell histiocytosis (LCH). It entails frank and open discussions with patients and their families of how the disease can affect them individually and collectively. Each point is explained and then applied to two different cases. The framework is applicable to all chronic pediatric diseases, but is particularly relevant for rare conditions with unknown etiologies such as LCH.

Triage: limitations in predicting need for emergent care and hospital admission.

STUDY OBJECTIVE: Little is known about the accuracy and reliability of current triage methods. We examined agreement among observers with regard to the need for ED care and the ability to predict at triage the need for admission to the hospital and compared these findings with admission rates after medical evaluation and management. METHODS: We used a crossover design in which each subject was subjected to nurse or computer-guided triage first, the other type of triage second, and physician triage last. Our null hypothesis: Triage methods will yield the same results. Our patients were a consecutive sample of patients at the ED of a university-affiliated county referral center. Critically ill patients were excluded. Triage categorization was examined for interobserver agreement (kappa-statistic) and prediction of admission (sensitivity, specificity, and predictive values). RESULTS: Of the 5,106 patients enrolled in the study, 289 (6.2%) were admitted. With regard to the agreement of triage categorizations, we found kappa-values of .452 and .185, respectively, for physician triage compared with nurse (SE +/- .012) and computer triage (SE +/- .012)(P = .001 for the difference between the kappa values). Sensitivity and specificity in predicting admission were 41.3 and 93.8, respectively, for nurses, 61.6 and 87.1, respectively, for physicians; and 68.2 and 73.6, respectively, for computer-aided triage. CONCLUSION: We found great variability among physicians, nurses, and a computer program with regard to triage decisions. Comparison of the three groups' triage decisions with actual data after medical evaluation and management showed that none of the three performed well in predicting which patients required admission. Until triage methods are standardized and validated, triage decisions should not be used to determine the timeliness of access to emergency care.

Nurses' perceptions of antiemetic effectiveness.

PURPOSES: To determine which antiemetics are being used with ondansetron (Zofran, Cerenex Pharmaceuticals, Research Triangle Park, NC) for patients receiving emetogenic chemotherapy, identify the more frequently administered antiemetic regimens, and ascertain nurses' perceptions of the effectiveness of these regimens. DESIGN: Descriptive survey. SETTING: Continental United States. SAMPLE: A random sample (N = 962) of Oncology Nursing Society members who designate themselves as practicing in the area of chemotherapy. METHODS: The Antiemetic Drug(s)/Drug Combination(s) Inventory, an open-ended questionnaire soliciting information on first- and second-line antiemetic regimens for emetogenic chemotherapy protocols, was mailed to 5,950 oncology nurses. Descriptive statistics and nondistributive analysis were used to analyze the data. FINDINGS: Ondansetron was used in 7 of 10 antiemetic regimens, which accounted for 50% of the most frequently used regimens. Nurses rated first-line antiemetic combinations as highly effective. Ondansetron alone was ranked as the seventh most effective first-line antiemetic for cisplatin protocols and fifth for noncisplatin protocols. Nurses noted limitations of ondansetron use, which included delayed nausea and vomiting and the drug's high cost. CONCLUSIONS: Study participants indicated that a variety of drugs were used in antiemetic regimens. Ondansetron use has improved the control of post-chemotherapy nausea, vomiting, and retching. IMPLICATIONS FOR NURSING PRACTICE: Antiemetics are administered regularly in the hospital and home to decrease chemotherapy-related nausea, vomiting, and retching. Managing these side-effects requires superior assessment skills and extensive knowledge of pharmacologic actions. Patient and family education on antiemetics is essential in light of increased administration of outpatient chemotherapy.

Intentional injury--homicide as a public health problem.

This article is an epidemiological analysis of Baltimore homicides between 1986 and 1990. The main findings were that young African-American males between 15 and 34 years of age are at greatest risk of homicide victimization. Homicidal events primarily occurred with handguns, in drug-related circumstances, between acquaintances, and in the western police district area. Questions are raised concerning the expansion of the public health professional's role and the use of epidemiologic data for injury prevention programs. This article is the result of a grant from the Centers for Disease Control and Prevention, Division of Injury Control, to the state of Maryland, Department of Health and Mental Hygiene, and the Baltimore City Health Department.

Comparison of prochlorperazine and lorazepam antiemetic regimens in the control of postchemotherapy symptoms.

This randomized, double-blind crossover study was undertaken to compare the antiemetic effectiveness of intravenous prochlorperazine (Compazine) and lorazepam (Ativan) in the management of postchemotherapy symptoms during two initial cycles of therapy. Each patient received at least one treatment as an outpatient. Data from the 24 patients receiving noncisplatin therapy who completed the crossover study were evaluated for antiemetic efficacy and total posttherapy symptom experience. Although results indicated no statistically significant difference between regimens in the control of posttherapy nausea and vomiting, these side effects were completely controlled in 26 of the 48 study treatment cycles. Lorazepam significantly reduced total posttherapy symptom experience by decreasing patients' experience of fatigue and pain. Findings support the value of lorazepam in antiemetic regimens and point to the need for further examination of antiemetic combinations.

Cancer control knowledge and priorities among primary care physicians.

Primary care physicians can play a key role in prevention and early detection of cancer. To assess cancer control knowledge and priorities among primary care physicians in Missouri, we conducted a random survey of 207 physicians. Although reported knowledge of the role tobacco plays in cancer causation was high, activity in tobacco cessation counselling and referral was low. Respondents considered diet to be a relatively unimportant factor in cancer causation, whereas they viewed sun exposure, genetics/family history, and radiation exposure as large contributors to the cancer burden. Among cancer early detection tests, high activity was shown for the Pap test and breast examination. Conversely, low activity was reported for colon sigmoidoscopy. Inverse correlations were shown between age group of the physician and several cancer prevention and early detection practices. For each cancer prevention and screening practice, reported activity was higher for medical doctors than for doctors of osteopathic medicine. Possible barriers or controversies in cancer control included disagreement with the current recommendation for Pap testing, the cost of mammography, and patient fear of sigmoidoscopy. These findings suggest that primary care physicians are not achieving their full potential in cancer control and indicate areas where increased emphasis is warranted.

Photolabeling of CheR methyltransferase with S-adenosyl-L-methionine (AdoMet). Studies on the AdoMet binding site.

CheR methyltransferase from Salmonella typhimurium was directly photolabeled with S-adenosyl-L-[methyl-3H]methionine. The labeled protein was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and then was detected by fluorography. The methylase-S-adenosyl-L-methionine adduct was found to be stable under the experimental conditions employed. Labeling was found to be a function of the concentration of enzyme, S-adenosyl-L-methionine (AdoMet), and the intensity and time of UV irradiation. The extent of labeling and protein methylation was found to be inhibited by S-adenosyl-L-homocysteine, S-adenosyl-L-ethionine, and sinefungin, which are known to compete with AdoMet for the same binding site on the enzyme. Our earlier data showed that the enzyme has 2 cysteine residues and that these are important for enzyme activity. Here, we show that sulfhydryl reagents inhibit the photolabeling of the substrate to the enzyme, indicating the presence of cysteine in the vicinity of the substrate-binding site. We also found that when Cys31 was modified to Ser, no photolabeling of CheR was observed, whereas a modification of Cys229 to Ser had little effect on the ability of AdoMet to label the enzyme. This suggests that Cys31 is located at or near AdoMet-binding site. The labeled protein was cleaved at tryptophan residues, generating two major fragments, each containing 1 cysteine residue. SDS-PAGE and fluorography of the cleaved products indicated the presence of the label being associated with the Cys31 fragment. Similar results were obtained when the labeled protein was cleaved at glutamic acid residues using V8 protease. A tryptic digest of the labeled protein showed two radioactive peptide peaks when subjected to separation on reverse phase high pressure liquid chromatography. The labeled peptides were further digested to free amino acids, and the labeled amino acid was identified as S-methylcysteine by thin layer chromatography. These results indicate that Cys31 may be involved with substrate binding, as well as with catalysis.

Probing the role of cysteine residues in the CheR methyltransferase.

The CheR methyltransferase catalyzes the transfer of methyl groups from S-adenosylmethionine to specific glutamyl residues in bacterial chemoreceptor proteins. Studies with sulfhydryl reagents such as p-chloromercuribenzoate, N-ethylmaleimide, and 5,5'-dithiobis(2-nitrobenzoate) suggest that a cysteine residue is required for enzyme activity. The nucleotide sequence of the cheR gene predicts a 288-amino acid protein with cysteine residues at positions 31 and 229. To ascertain the role of these cysteine residues in the structure and function of the enzyme, oligonucleotide-directed mutagenesis was used to change each cysteine to serine. Whereas the Cys229-Ser mutation had essentially no effect on transferase activity, the Cys31-Ser mutation caused an 80% decrease in enzyme activity. The double mutant in which both cysteines were replaced by serines also had markedly reduced transferase activity. Preincubation of the wild type or Cys229-Ser proteins with either S-adenosylmethionine or beta-mercaptoethanol protected it from inhibition by sulfhydryl reagents, whereas prior incubation with the second substrate, the Tar receptor, gave partial protection. From these studies, Cys31 appears to be necessary for enzyme activity, and it seems to be located in the vicinity of the active site.

The kinetic mechanism of S-adenosyl-L-methionine: glutamylmethyltransferase from Salmonella typhimurium.

The kinetic mechanism of the CheR methyltransferase, S-adenosyl-L-methionine (AdoMet): protein-L-glutamate O-methyltransferase (EC 2.1.1.24), from Salmonella typhimurium was investigated. Initial velocity, product inhibition, and binding studies were performed, and from the data obtained, it was determined that the mechanism of the reaction catalyzed by the enzyme is random. Initial velocity rates were measured with varied amounts of both substrates, and double-reciprocal plots gave patterns which converged on or near the abscissa. The products, S-adenosyl-L-homocysteine and methylated receptor, were found to be competitive inhibitors with respect to both AdoMet and receptor. Equilibrium dialysis and immunoprecipitation studies indicated that the two substrates can bind to the enzyme independent of each other. These results are consistent with a random mechanism with no abortive complexes being formed. The Michaelis constants calculated for AdoMet and receptor were 8.62 microM and 2.03 mg/ml total membrane protein (approximately 2.10 microM Tar protein), and the apparent dissociation constants of AdoMet and the receptor were 16.8 microM and 4.07 mg/ml total membrane protein (approximately 4.2 microM Tar protein), respectively. The Kd of AdoMet for the enzyme was 10.9 microM as determined by binding studies.

Merging expertise and resources for research.

Nurse educators and nurse administrators share an interest in research. When a group of nursing administrators identified a need for research in their community hospital, a collaborative effort was initiated with a nurse educator from a nearby school of nursing. The successful collaborative effort proceeded through the four stages as identified by Keefe, Pepper, and Stoner (1988): Initiation, generation, incorporation, and validation. The activities and outcomes of each stage are described. The results of the collaborative effort were positive, creating advantages for all involved.

Emphysematous gastritis: case report and review.

Emphysematous gastritis is a condition involving gastric wall inflammation, radiologic or intraoperative evidence of intramural gas, and systemic toxicity. A recent case of emphysematous gastritis in a 57-year-old diabetic man is reported, and 27 cases published since 1889 are reviewed. Predisposing factors include ingestion of corrosive substances (37%) and alcohol abuse (22%). Diagnosis of emphysematous gastritis is based on the clinical presentation of an acute abdomen with systemic toxicity and on radiographs demonstrating gas bubbles within the stomach wall. For the case reported herein, computed tomography was useful both in establishing the diagnosis and in following the resolution of emphysematous gastritis. Organisms most commonly involved were Escherichia coli (six cases), Streptococcus species (six cases), Enterobacter species (five cases), and Pseudomonas aeruginosa (three cases). The mortality was 61% (17 of 28 patients), and morbidity with gastric contractures occurred in 21% of cases (6 of 28). Optimal therapy has not been defined; however, antimicrobial chemotherapy and surgery, when appropriate, may improve survival rates.