Quality of life as conveyed by pediatric patients with cancer.

Quality-of-life instruments have provided important advances in measuring the quality of life of pediatric patients receiving treatment for cancer. However, the bases of these instruments have not included first-hand reports from the patients; thus, these instruments may be conceptually incomplete. We directly solicited from pediatric patients their perspectives regarding their quality of life during treatment for cancer. We conducted two pilot studies: 23 patients (aged 8-15 years) participated in the first, a cross-sectional study; and 13 patients (aged 10-18 years) participated in the second, a 2-year longitudinal study. Data were analyzed by using a semantic-content method, and the following six domains were recognized in data from both of the studies: symptoms, usual activities, social/family interactions, health status, mood, and the meaning of being ill. These domains were compared with those of seven established pediatric oncology quality-of-life instruments, none of which included all six of these domains; the domain most frequently missing was the meaning of being ill domain. Here we present a new definition of the quality of life of pediatric oncology patients that is based on six domains; this definition may ensure the completeness and sensitivity of these important instruments.

Acute health-related quality of life in children undergoing stem cell transplant: I. Descriptive outcomes.

There has been little empirical documentation of the acute effects of bone marrow or stem cell transplant (BMT) on children. In the present study, the responses of 153 children undergoing BMT were assessed in a prospective, longitudinal design. Children were assessed at the time of admission for transplant, then underwent weekly assessments to week +6, followed by monthly assessment to month +6. Data were obtained both by parent report and patient report (for patients age 5 and up) using the BASES scales. The major findings are: (1) children undergoing BMT enter the hospital with an already heightened level of distress (defined by high levels of somatic symptoms and mood disturbance, and low levels of activity) that increases dramatically following conditioning, reaching a peak approximately 1 week following transplant; (2) this increased distress is transient, declining rapidly back to admission levels by week +4 to week +5, followed by a further decline to presumed basal levels by months 4-6; and (3) the trajectories of distress depicted by both parent and child report are remarkably similar, each providing confirmatory support for the validity of the findings. These findings confirm a number of widely held clinical impressions that had not previously been documented empirically, and point to the need for new interventions or more intensive approaches to supportive care aimed at reducing levels of distress during the acute phase of transplant.

Acute health-related quality of life in children undergoing stem cell transplant: II. Medical and demographic determinants.

Medical and demographic variables were examined as predictors of acute health-related quality of life (HRQL), specifically, somatic distress, mood disturbance and activity levels, during the period of bone marrow transplant (BMT) hospitalization, and the transition phase in the months following hospital discharge. The responses of 153 children undergoing BMT were assessed by both parent report and patient self-report in a prospective longitudinal design. Type of transplant, diagnosis, age, gender, and socio-economic status (SES) were examined as predictor variables of patient outcome. Type of transplant, patient age, and SES emerged as significant determinants of patient response. Children undergoing unrelated donor (MUD) transplants experiencing the highest levels of distress, followed by those undergoing matched-sibling BMT, while those undergoing autologous transplant experienced the lowest levels of distress. Younger patients experienced lower levels of distress and better HRQL than older children and adolescents. Although patients from different SES backgrounds appeared very similar at the time of hospital admission, those from lower SES backgrounds demonstrated greater distress and disturbance in HRQL subsequently, and throughout the first 6 months post BMT. These findings help to target specific subgroups of patients that may be in greater need of preventive interventions or more aggressive supportive care.

Diets containing whey proteins or soy protein isolate protect against 7,12-dimethylbenz(a)anthracene-induced mammary tumors in female rats.

A study was conducted to determine the protective effects of two common dietary proteins, soy protein isolate (soy) and bovine whey, against chemically induced mammary tumors in female Sprague Dawley rats. Rats were fed AIN-93G diets having casein, soy, or whey as the sole protein source. Rats within the same dietary groups were mated to obtain the F1 and F2 generations. At age 50 days, F1 (experiment A) or F2 (experiment B) female offspring (> or =19 rats/group) were p.o. gavaged with 80 mg/kg 7,12-dimethylbenz(a)anthracene, and mammary glands were evaluated when 100% of the casein-fed group developed at least one palpable tumor. Rats grew well on all three diets, but casein-fed rats gained slightly more body weight than soy- or whey-fed rats (P < 0.05). Vaginal opening occurred 1 day earlier in soy-fed rats than in casein- or whey-fed rats, but no other differences in reproductive and developmental parameters were observed between groups. When 50% of the casein-fed rats had at least one mammary tumor, lower tumor incidences (24-34%) were observed in the soy-fed (P < 0.009) and whey-fed groups (P < 0.001). When 100% of the casein-fed rats had at least one tumor, soy-fed rats had a lower tumor incidence (77%) in experiment B (P < 0.002), but not in experiment A (P < 0.12), and there were no differences in tumor multiplicity. Whey-fed rats had lower mammary tumor incidence (54-62%; P < 0.002) and multiplicity (P < 0.007) than casein-fed rats in both experiments. Our results indicate that diets rich in soy reduce the incidence of chemically induced mammary tumors by approximately 20%. Furthermore, whey appears to be at least twice as effective as soy in reducing both tumor incidence and multiplicity.

High fever after flexible bronchoscopy and bronchoalveolar lavage in noncritically ill immunocompetent children.

Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) have been applied increasingly to the evaluation of pulmonary disease in children. Although several complications have been reported following FB and BAL, high fever after BAL in immunocompetent children has not previously been reported. To determine the frequency, clinical characteristics, and outcome of these complications in children who developed high fever post-BAL, we retrospectively reviewed all bronchoscopic procedures done on an outpatient basis between August 1995 and July 1997. We identified 78 immunocompetent noncritically ill children who had undergone FB and BAL as an outpatient procedure for evaluation of underlying pulmonary disease, of whom 13 (17%) developed temperature (T) higher than or equal to 39 degrees C (fever group). The 13 patients in the fever group had a median age of 10 (range, 4-48) months and a reported T of 39.4 degrees C (39.1-40.6 degrees C) occurring 7.5 (4-12) hr after BAL. To determine if there were differences in clinical or BAL fluid (BALF) characteristics, we compared each child in the fever group to two children in the nonfever group, based upon primary indications and age. There were no differences in demographic or clinical characteristics between the two groups. Lymphocyte concentrations in BALF were significantly reduced in the fever group (P = 0.03). An abnormal BALF cell differential (defined as one or more of the following: neutrophils >10%, lymphocytes >30%, or eosinophils >1%) was significantly more common in the fever group (P = 0.008, odds ratio 3.6). We conclude that high fever is a frequent adverse event following BAL in noncritically ill immunocompetent children with underlying pulmonary disease. Pre-BAL clinical characteristics are not associated with development of high fever. However, the finding of an abnormal BALF cell differential is strongly associated with development of high fever post-BAL.

Clinical utility of flexible bronchoscopy and bronchoalveolar lavage in young children with recurrent wheezing.

OBJECTIVE: The objective of this study was to determine in young children with recurrent wheezing poorly responsive to bronchodilator therapy whether flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) provide clinically useful information, whether age-specific differences are present in bronchoscopic and BAL fluid (BALF) findings, and whether differential cellular analysis of BALF is useful in suggesting an infectious or inflammatory process. DESIGN: This was a retrospective case series with descriptive and analytical components. The study population included children referred to a large tertiary care children's hospital subspecialty service for further evaluation of recurrent wheezing. Clinical and demographic data and findings of FB and BALF studies were collected from chart review. For purposes of data analysis patients were divided into 0- to 6-, 7- to 12-, and 13- to 18-month age groups. RESULTS: Thirty otherwise healthy children, 0 to 18 months of age with recurrent wheezing, who had undergone FB were identified; and 28 were found to have positive diagnostic findings. Airway abnormalities were found in 17 (57%) and tended to be more common in the 0- to 6-month age group. In the 27 who also had BAL performed, 3 (11%) had a positive bacterial culture, 9 (33%) a positive viral culture, and 5 (19%) an elevated lipid-laden macrophage index suggesting aspiration. Differential cellular analysis was abnormal in 11 (41%), a finding that was significantly associated with a positive bacterial culture, a positive viral culture, or an elevated lipid-laden macrophage index. CONCLUSIONS: In this population of young children with recurrent wheezing poorly responsive to bronchodilator therapy, FB and BAL yielded useful diagnostic findings in most children studied. In addition, in the presence of an infectious or inflammatory process, differential cellular analysis of BALF revealed an increased percentage of neutrophils.

In vivo antimutagenic activity of beta-carotene in rat spleen lymphocytes.

The anticarcinogenic effects of beta-carotene (BC) have been extensively investigated, but only in vitro assays have examined the ability of BC to modulate gene mutation. In view of the current interest in the provitamin as a cancer chemopreventive agent, and the association between mutagenesis and carcinogenesis, we have dosed Fischer 344 rats with model carcinogen N-ethyl-N-nitrosourea (ENU) and investigated the relationships among BC intake, its tissue accumulation, and antimutagen activity. Animals received drinking water supplemented with BC at doses of 0-0.25% ad libitum, using three dosing schedules. In one group BC dosing commenced before, and continued for three alternating weeks after i.p. injection of 100 mg ENU/kg; another group was given BC only after mutagen treatment. Animals from the first two groups were sacrificed 5 weeks post-mutagen treatment, and cells were isolated from the spleen to determine the frequency of 6-thioguanine- resistant (6-TGr) T-lymphocytes. The presence of BC caused a reduction in the frequency of 6-TGr T-cells produced by ENU, but the inhibition was non-linear within the range of BC doses used. BC intake only after mutagen treatment was more effective than the combination of pre- and post-mutagen intake. In the third group, rats were treated with 100 mg ENU/kg, and BC administration was continued at a fixed dose of 0.15% in the drinking water for 2, 4, 6, or 8 weeks. Measurement of the frequency of 6-TGr T-cells at the end of the specified times showed > 50% reduction in ENU-mediated mutagenicity throughout the experiment. Analysis of BC levels in the liver and in the spleen following BC intake before and during mutagen exposure revealed higher levels than when BC was given only after mutagen treatment. Continuous intake of BC also showed increased tissue levels. There were some correlations observed between BC tissue levels and the antimutagenic effects for the first two groups, but these correlations were not statistically significant, possibly due to the small numbers of animals used. Taken together, the results demonstrate that intact BC is absorbed, stored, and exerted antimutagenic effects against a chemical carcinogen in rats without first being transformed to retinol in the gastrointestinal tract.

Fitting the two-stage clonal expansion model based on exact hazard to the ED01 data using SAS NLIN.

The two-stage clonal expansion model is a popular model for carcinogenesis data. One common form of this model is based on the approximate hazard function. In certain situations, this formulation is not appropriate, and the exact hazard should be applied. However, the difficulty of implementing the model based on the exact hazard has deterred many from using it. This paper presents a program implementing the exact hazard model for piecewise constant dosing using SAS, a package that is readily available to most that are interested in this type of analysis. Also, an analysis of the ED01 data is presented using this program, and comparisons are made to an earlier analysis based on the approximate hazard. By allowing for an independent background tumor mechanism, an excellent fit to the bladder tumor incidence data was obtained.

Ascorbic acid (vitamin C) modulates the mutagenic effects produced by an alkylating agent in vivo.

Recent reports suggest that ascorbic acid (vitamin C) inhibits tumorigenesis as well as exerts a protective effect against mutagenesis in vitro; however, there is no information on its ability to affect gene mutations induced in vivo. In this study, we have investigated the antimutagenic effects of ascorbic acid on the frequency of 6-thioguanine-resistant (6-TGr) T-lymphocytes produced in Fischer 344 rats dosed with the direct-acting alkylating agent, N-ethyl-N-nitrosourea (ENU). The frequency of 6-TGr T-lymphocytes from the spleen measured five weeks after ENU treatment indicated that ENU produced a substantial mutagenic response. Pretreatment and/or post-treatment of rats with ascorbic acid administered in the drinking water appeared to inhibit the response, but the inhibition was statistically significant only when data from the various dosing schedules were pooled. In addition, there was no clear dose-dependency to the inhibitory effect of ascorbic acid. To further evaluate the time effects of the vitamin supplement on ENU mutagenicity, rats were exposed to the mutagen together with ascorbic acid, which was given continuously for the entire duration of the experiment. At specific times after ENU treatment, the frequency of 6-TGr T-cells was determined in lymphocytes isolated from the spleen and the thymus. Time-dependent increases in the frequency of 6-TGr T-cells were observed with ENU treatment; ascorbic acid significantly reduced the ENU-mediated mutagenic responses, most dramatically in the spleen at weeks 6 and 8 (P < 0.0001), and to a lesser extent in the thymus (P < 0.01 at week 6 and P < 0.006 at week 8). Our data suggest that ascorbic acid intake affects the in vivo mutagenicity of ENU, a direct-acting mutagen/carcinogen, and that the reported inhibitory effects of the antioxidant on carcinogenesis may be partially mediated by its effects on mutagenesis. Although it is difficult to extrapolate from rodent studies to humans, the results presented suggest an explanation for epidemiological data that link vitamin C ingestion with decreased cancer risk.