Psychological effects of bone marrow transplantation on children and adolescents: preliminary report of a longitudinal study.

The number of pediatric bone marrow transplantation (BMT) survivors is growing rapidly, yet little is known about the long-term neuropsychologic and psychosocial sequelae of this procedure. Using a prospective, longitudinal design, 64 pediatric patients undergoing BMT were evaluated with standardized measures of global intelligence, academic achievement and selected tests of neuropsychologic function. In addition, adjustment was assessed with parent and patient report measures of social competence, behavior problems and self-esteem. Patients were evaluated prior to admission for BMT, and again in the period 6-12 months after BMT. Longitudinal findings are reported on an initial cohort of 25 survivors. Cognitive and neuropsychologic function remained stable during the study period. The few significant changes from baseline which were observed were in the direction of improvement, and may be attributed to practice effects. In contrast, declines were observed in patient social competence, self-esteem and general emotional well-being. BMT conditioning regimens appear not to be associated with significant neuropsychologic impairment in the first year after transplant. However, a longer period of follow-up is necessary before neuropsychologic late-effects can be ruled out. The first year after BMT is characterized by significant psychosocial difficulties for survivors. Adjustment issues may provide a more salient focus of study during this time frame.

Adenovirus infection after pediatric bone marrow transplantation.

Retrospective analysis of 206 patients undergoing 215 consecutive bone marrow transplants (BMT) at St Jude Children's Research Hospital between November 1990 and December 1994 identified 6% (seven male, six female) with adenovirus infection. The affected patients had a median age of 7.9 years (range 3-24 years) at time of transplantation. Although transplants were performed for hematologic malignancies, solid tumors or nonmalignant conditions, only patients with hematologic malignancies had adenoviral infections. Adenovirus was first detected at a median of 54 days (range -4 to +333) after BMT. Adenovirus developed in eight of 69 (11.6%) patients receiving grafts from matched unrelated or mismatched related donors, in four of 52 (7.7%) receiving grafts from HLA-matched siblings, and in one of 93 (1.1%) receiving autografts. The most common manifestation of adenovirus infection was hemorrhagic cystitis, followed by gastroenteritis, pneumonitis and liver failure. The incidence of adenovirus infection in pediatric BMT patients at our institution is similar to that reported in adult patients. Using univariate analysis, use of total body irradiation and type of bone marrow graft were significant risk factors for adenovirus infection. Only use of total body irradiation remained as a factor on multiple logistic regression analysis.

The effect of N-terminal acetylation and the inhibition activity of acetylated enkephalins on the aminopeptidase M-catalyzed hydrolysis of enkephalins.

High performance liquid chromatography and high performance liquid chromatography/electrospray ionization-mass spectrometry were used to study the effect of N-terminal acetylation and the inhibition activity of acetylated enkephalins on the aminopeptidase M (EC 3.4.11.2)-catalyzed hydrolysis of methionine (Met-enk) and leucine enkephalins (Leu-enk). Acetylation imparts a significant enhancement in the proteolytic stability of these two peptides. After 30 min of the reaction, < 10% of both acetylated enkephalins was hydrolyzed. In an 8-h incubation period, only a maximum of 54% acetylated (Ac)-Met-enk and 38% Ac-Leu-enk was hydrolyzed. Vmax and Km [infil] for the degradation of Ac-Met-enk were 1.4 nmol/min/50 ng and 2.2 mM, respectively. The corresponding values for the reaction of Ac-Leu-enk were 0.5 nmol/min/50 ng and 0.9 mM. Also, the aminopeptidase M activity on Met-enk can be inhibited in the presence of Ac-Met-enk, which acts as a mixed-type inhibitor with the inhibition constant (K(i)) of I x 10(-3) M.

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.

Efficacy of inactivated H5N2 influenza vaccines against lethal A/Chicken/Queretaro/19/95 infection.

The control and eventual eradication of H5N2 influenza virus from domestic poultry in Mexico is dependent on the use of avian influenza (AI) vaccine strategies. This study was performed to determine the amount of hemagglutinin (HA) antigen required to control the signs of disease from a highly pathogenic H5N2 influenza virus (A/Chicken/ Queretaro/19/95) and the amount of antigen required to prevent shedding of virus from vaccinated birds. Six commercial inactivated water in oil H5N2 vaccines available in Mexico were compared with standardized vaccines to assess their efficacy. The amount of HA required to prevent the signs of disease from A/Chicken/Queretaro/19/95 influenza virus was approximately 0.4 microgram per dose. Each of the six commercially available vaccines prevented disease signs, and half of the vaccines significantly reduced viral shedding from vaccinated birds. There is a need for standardization of AI virus vaccine, and the antigen content should be increased in some of the commercially available AI vaccines in Mexico.

Decision making by parents and healthcare professionals when considering continued care for pediatric patients with cancer.

PURPOSE/OBJECTIVES: To better define the treatment-related decisions considered most difficult by parents of pediatric patients with cancer and the factors that influenced their final decisions. DESIGN: Retrospective-descriptive design. SETTING: Pediatric oncology institution in the mid-southern region on the United States. SAMPLE: 39 parents representing 37 of 83 eligible families, 16 attending physicians, three nurses, and two chaplains. METHODS: Parent participants responded by telephone to six open-ended interview questions and a 15-item questionnaire about factors that were important when making the decision to continue care. Healthcare professionals were interviewed face-to-face. MAIN RESEARCH VARIABLES: Most difficult treatment-related decisions; factors influencing decision making. FINDINGS: Parents reported 15 types of difficult decisions, the majority of which were made late in the course of treatment. Deciding between a phase I drug study or no further treatment (n = 14), maintaining or withdrawing life support (n = 11), and giving more chemotherapy or giving no further treatment (n = 8) were the most frequently reported difficult decisions. Parents rated "recommendations received from healthcare professionals" as the questionnaire factor most important in their decision making, and healthcare professionals rated "discussion with the family of the patient" as the most important factor. CONCLUSION: Parents of children or adolescents with cancer and their healthcare providers face difficult treatment-related decisions, many of which occur late in the course of treatment. Parents and healthcare professionals cite similar factors in their decision making but differ in their ratings of the factors' importance. For parents, the information and recommendations they receive from healthcare professionals figure most frequently and most importantly in their decision making. For healthcare professionals, the certainty that the patient will not get better and discussions with the patient's family figure most importantly in their decision making. Once parents conclude that their child can not get better, they are more likely to choose noncurative options such as choosing no further treatment or withdrawing life support. IMPLICATIONS FOR NURSING PRACTICE: Nurses can help determine what information parents need in their decision making. Particular attention must be given to ways to communicate the likelihood of the their child's survival.

A randomized, double-blind trial to evaluate immunogenicity and safety of 13-valent pneumococcal conjugate vaccine given concomitantly with trivalent influenza vaccine in adults aged ≥65 years.

This randomized, double-blind study evaluated concomitant administration of 13-valent pneumococcal conjugate vaccine (PCV13) and trivalent inactivated influenza vaccine (TIV) in adults aged ≥65 years who were naïve to 23-valent pneumococcal polysaccharide vaccine. Patients (N=1160) were randomized 1:1 to receive PCV13+TIV followed by placebo, or Placebo+TIV followed by PCV13 at 0 and 1 months, with blood draws at 0, 1, and 2 months. Slightly lower pneumococcal serotype-specific anticapsular polysaccharide immunoglobulin G geometric mean concentrations were observed with PCV13+TIV relative to PCV13. Concomitant PCV13+TIV demonstrates acceptable immunogenicity and safety compared with either agent given alone.

Assessment of health-related quality of life in acute in-patient settings: use of the BASES instrument in children undergoing bone marrow transplantation.

The Behavioral, Affective and Somatic Experiences Scale (BASES) represents a set of tools for assessing aspects of health-related quality of life (HRQL) in patients undergoing active, intensive therapy. Separate versions have been developed for parent, nurse and patient reports. The scales were constructed to be sensitive to change and appropriate for repeated measures in longitudinal designs. We report preliminary results with these measures from a sample of 105 children undergoing bone marrow transplantation (BMT). Adequate reliability of the instruments is documented through measures of both internal consistency and cross-informant consistency. Several analyses provide evidence of the clinical validity of the measures. Repeated-measures ANOVAs indicated reliable patterns of change over time, with trajectories that conformed to a priori predictions. Discriminative validity was demonstrated through detection of significant differences in the predicted direction between patients undergoing allogeneic and autologous BMT. Additional evidence for validity comes from the very similar symptom trajectories in parent, nurse and patient reports. Differences between the BASES and other measures of HRQL are identified and alternative uses of the instruments are discussed.

A single injection of pegylated murine megakaryocyte growth and development factor (MGDF) into mice is sufficient to produce a profound stimulation of megakaryocyte frequency, size, and ploidization.

Despite numerous studies investigating the action of c-mpl ligand, no reports have defined the in vivo changes in megakaryocytopoiesis in response to a single injection of this cytokine. Here we compare the kinetics of the megakaryocytopoietic response in C57BI/6J mice administered 25 micrograms/ kg or 250 micrograms/kg of pegylated (PEG) murine megakaryocyte growth and development factor (MGDF) as a single intravenous injection. Megakaryocytes of mice treated with MGDF had normal ultrastructure, showing a typical distribution of the demarcation membrane system, alpha-granules, and other cytoplasmic organelles. Megakaryocyte ploidy, size, and frequency were markedly increased with both MGDF doses. Megakaryocyte ploidy was maximally increased from a modal value of 16N to 64N on day 3, with both doses of MGDF. Similarly, a comparable increase in megakaryocyte size occurred in the two MGDF groups. Increased megakaryocyte size was coupled to the increase in megakaryocyte ploidy, and no evidence for independent regulation of megakaryocyte size within individual ploidy classes was apparent. In contrast to megakaryocyte ploidy and size, the increase in megakaryocyte frequency was markedly different with the two doses of MGDF. The proportion of 2N and 4N cells was increased from a baseline of 0.035% to 0.430% by day 4 in mice treated with the higher dose of MGDF, but only to 0.175% in mice administered 25 micrograms/kg of MGDF. The marked increase in the pool of these immature megakaryocytes translated to a sustained elevation in the frequency of polyploid megakaryocytes (8N cells and greater). In contrast to the sustained increase in the frequency of polyploid cells, the level of polyploidization was downregulated on days 6 to 10, but normalized by day 14. We conclude that a single injection of MGDF is able to expand the megakaryocytic pool in a dose-dependent manner, which, with subsequent maturation, should lead to an increased rate of platelet production.

A single intravenous dose of murine megakaryocyte growth and development factor potently stimulates platelet production, challenging the necessity for daily administration.

The thrombopoietic efficacy of recombinant forms of c-mpl ligand is being actively investigated in preclinical studies using daily dosing schedules. However, a comprehensive kinetic study of the thrombopoietic response to a single injection of recombinant c-mpl ligand has not been performed. Here, we present the results of a detailed kinetic analysis of the platelet response to a single intravenous administration of pegylated recombinant murine megakaryocyte growth and development factor (PEG-rmMGDF) in mice. In addition, we compare the efficacy of single versus daily dosing in stimulating platelet production. A single intravenous injection of PEG-rmMGDF produced a marked and dose-dependent elevation in platelet number and a moderate increase in mean platelet volume (MPV). After administration of 25 or 250 micrograms/kg of PEG-rmMGDF, platelet number was first increased on day 3 and peaked at 2.7-fold (25 micrograms/kg) and 5.7-fold of normal (250 micrograms/kg) on day 5. Thereafter, platelet number declined and returned to baseline by days 9 and 14, with the 25 and 250 micrograms/kg doses, respectively. MPV began to increase on day 2 after PEG-rmMGDF, reaching maximum values of 1.2-fold (25 micrograms/kg) and 1.5-fold of normal (250 micrograms/kg) on day 4. Subsequently, MPV declined and was downregulated on days 6 to 7 (25 micrograms/kg) and day 8 (250 micrograms/kg). Based on these results, we evaluated the platelet response to PEG-rmMGDF administered intravenously as a single dose versus daily for 5 days. A single administration of 100 micrograms/kg produced a higher platelet number on day 5 than daily administration of 100 or 20 micrograms/kg for 5 days. However, the thrombocytosis was less sustained after single versus daily dosing. The smaller platelet number increase on day 5 after daily dosing reflected the production of larger platelets, rather than suppression of thrombopoiesis. Our results indicate that PEG-rmMGDF administered as a single intravenous dose potently stimulates platelet production in mice, challenging the need for its daily administration. Adoption of an intermittent administration schedule of this cytokine could be more efficacious and is merited in future clinical trials.

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.

Testing the stress-response sequence model in paediatric oncology nursing.

The causes and intensity of role-related stress experienced by paediatric oncology nurses, the nurses' ability to respond to the stressors, and the professional and personal consequences of those stressors for the nurses are issues of concern for administrators and staff. The concern evolves from the anticipated relationships among stressors, the ability to cope with role-related stressors, and the expected negative outcomes such as resignation. However, the relationships among these components have not been previously measured concurrently in paediatric oncology nurses. The primary purpose of this study was to test the complete stress-response sequence model in a sample of paediatric oncology nurses by obtaining concurrent measures of the model's individual components: nurses' stressors, reactions, mediators, and consequences. A total of 126 nurses completed six questionnaires (Stressor Scale for Paediatric Oncology Nurses, Perceived Stress Scale, Measure of Job Satisfaction, Organized Commitment Questionnaire, Group Cohesion Scale, and Intent to Leave) and a demographic sheet. The majority of participating nurses were married, worked full-time and had worked 5 or more years in oncology. Qualitative data were analysed using a semantic content analysis technique. Relationships among the components of the model were examined using a two-stage least squares technique. The components were only weakly associated and unable to explain significant variation in each other. The combined qualitative and quantitative data indicate that an important explanatory variable - role-related meaning - is missing in the content model.