Health-related quality of life and well-being in parents of infants and toddlers with cancer.

Background: The unique psychosocial needs of parents and caregivers of young children with cancer are poorly understood. The aims of the present study were to examine health-related quality of life (hrqol), stress, and psychological distress in parents of young children (0-4 years) diagnosed with cancer; and the associations between parent psychosocial functioning and child treatment characteristics. Methods: Parents (n = 35) with a child (n = 19 male, 54.3%) 0-48 months of age (median: 31.06 months) on active cancer therapy were recruited. Parents completed questionnaires related to demographics, parent hrqol, parenting stress, posttraumatic stress symptoms, and parent psychological distress. Results: Parents reported clinically elevated parenting stress (5.9%), posttraumatic stress symptoms (18.2%), and psychological distress (21.9%). Compared with population norms, parents reported lower hrqol in the vitality (t = 5.37, p < 0.001), mental health (t = 4.02, p < 0.001), role limitation-emotional (t = 3.52, p < 0.001), and general health perceptions (t = 2.25, p = 0.025) domains. Social functioning (ß = 0.33, p = 0.041) predicted general health perceptions; vitality (ß = 0.30, p = 0.134) and parent mental health (ß = 0.24, p = 0.285) did not [F(3,29) = 12.64, p < 0.001, R2 = 0.57]. Conclusions: A subset of parents of young children on active cancer treatment experience clinically elevated psychosocial symptoms. Having poor social connections put parents at risk of perceiving their health more poorly in general. Supports that focus on preventing the emergence of clinically significant distress should focus on parents of young children with cancer who are most at risk of poor outcomes.

A comparison of two models of follow-up care for adult survivors of childhood cancer.

PURPOSE: Few studies have compared follow-up-care models for adult survivors of childhood cancer (ASCCs), though choice of model could impact medical test adherence, and health-related quality of life (QOL). This study compared two follow-up-care models, cancer-center-based versus community-based, for ASCCs in Alberta, Canada, to determine which model would demonstrate greater ASCC adherence to guideline-recommended medical screening tests for late effects, QOL, physical symptoms, and adherence to yearly follow-up. METHODS: ASCC discharged to a community model (over 15 years) and those with comparable birth years (1973-1993) currently followed in a cancer center model were recruited via direct contact or multimedia campaign. Chart review identified chemotherapeutic and radiation exposures, and required medical late effect screening tests. ASCCs also completed questionnaires assessing QOL, physical symptoms, and follow-up behavior. RESULTS: One hundred fifty-six survivors participated (community (n = 86); cancer center (n = 70)). Primary analysis indicated that cancer center ASCCs guideline-recommended total test adherence percentage (Mdn = 85.4%) was significantly higher than the community model (Mdn = 29.2%, U = 3996.50, p < 0.0001). There was no significant difference in QOL for cancer center ASCCs (M = 83.85, SD = 20.55 versus M = 77.50, SD = 23.94; t (154) = 1.77, p = 0.078) compared to community-based ASCCs. Cancer center-based ASCCs endorsed from 0.4-7.1% fewer physical symptom clusters, and higher adherence to follow-up behavior in comparisons using effect sizes without p values. CONCLUSION: This study highlights the cancer center model's superiority for adherence to exposure-based medical late effect screening guidelines, cancer-specific follow-up behaviors, and the reporting of fewer physical complaints in ASCCs. IMPLICATIONS FOR CANCER SURVIVORS: ASCCs followed in a cancer center model likely benefit from earlier late-effects detection and opportunities for early intervention.

Quality of life in pediatric cancer survivors: contributions of parental distress and psychosocial family risk.

BACKGROUND: Pediatric survivors of childhood cancer are at increased risk of poor quality of life and social-emotional outcomes following treatment. The relationship between parent psychological distress and child adjustment in pediatric cancer survivors has been well established. However, limited research has examined the factors that may buffer this association. The current study examined the associations between psychosocial family risk factors, parental psychological distress, and health-related quality of life (hrql) in pediatric cancer survivors. METHODS: Fifty-two pediatric cancer survivors (34 males, 18 females, mean age = 11.92) and their parents were recruited from a long-term cancer survivor clinic. Children and their parents who consented to participate completed the Pediatric Quality of Life Inventory 4.0. Parents completed a demographic information form, the Psychosocial Assessment Tool (pat 2.0) and the Brief Symptom Inventory (bsi). The Intensity of Treatment Rating (itr-3) was evaluated by the research team. RESULTS: Multiple regression analyses revealed that parental psychological distress negatively predicted parent-reported hrql, while treatment intensity, gender, and psychosocial risk negatively predicted parent and child-reported hrql. Psychosocial risk moderated the association between parent psychological distress and parent-reported child hrql (p = 0.03), whereby parents with high psychological distress but low levels of psychosocial risk reported their children to have higher hrql. CONCLUSION: Low levels of family psychosocial risk buffer the impact of parent psychological distress on child hrql in pediatric cancer survivors. The findings highlight the importance of identifying parents and families with at-risk psychological distress and psychosocial risk in order to provide targeted support interventions to mitigate the impact on hrql.

Effects of chenodeoxycholic acid on the secretion of gut peptides and fibroblast growth factors in healthy humans.

CONTEXT: Recent evidence suggests bile acids (BAs) are involved in the glycemic control via TGR5 activation with the subsequent release of gut peptides and farnesoid X receptor activation with ensuing release of fibroblast growth factors (FGFs). OBJECTIVE: We hypothesized that intraduodenal infusions of chenodeoxycholic acid (CDCA) would stimulate FGF and gut peptide secretion, thereby positively influencing glucose homeostasis. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: This randomized, double-blind, placebo-controlled, crossover trial included 12 healthy volunteers who received intraduodenal infusions (2.0 mL/min for 180 minutes) of saline, CDCA (5 or 15 mmol/L), and a fatty acid (sodium oleate), either alone or with 5 mmol/L CDCA. After 60 minutes, an oral glucose tolerance test (oGTT) was performed. MAIN OUTCOME MEASURES: Plasma levels of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine, cholecystokinin (CCK), total BAs, FGF19, FGF21, C-peptide, insulin, glucose, and glucagon were measured. RESULTS: Within the first 60 minutes, high-concentration CDCA induced a small but significant increase in GLP-1 and CCK secretion (P = .016 and P =.011), whereas plasma C-peptide, insulin, and glucose were not affected. Attenuated C-peptide and insulin release was observed after the oGTT with 15 mmol/L CDCA (P = .013 and P =.011). Plasma BA and FGF19 levels significantly increased after CDCA administration (P = .001 and P < .001). CONCLUSIONS: CDCA modulates GLP-1 and CCK secretion; the effect is small and does not influence glucose levels. The marked increase in plasma BAs and the attenuated insulin release after the oGTT indicate the role of BAs in glycemic control, independent of the incretin axis, and suggest involvement of farnesoid X receptor activation pathways.

Longitudinal in vivo imaging of bone formation and resorption using fluorescence molecular tomography.

Bone research often focuses on anatomical imaging of the bone microstructure, but in order to gain better understanding in how bone remodeling is modulated through interventions also bone formation and resorption processes should be investigated. With this in mind, the purpose of this study was to establish a longitudinal in vivo imaging approach of bone formation and resorption using fluorescence molecular tomography (FMT). In this study the reproducibility, accuracy and sensitivity of FMT for bone imaging were assessed by performing longitudinal measurements with FMT and comparing it to in vivo micro-computed tomography on a set of control mice, and mice in which load-adaptation was induced in the sixth caudal vertebra. The precision error for FMT measurements, expressed as coefficient of variation, was smaller than 16%, indicating acceptable reproducibility. A correlation was found between bone resorption measured with FMT and bone resorption rate measured with in vivo micro-computed tomography only over the first 14days (R=0.81, p<0.01), but not between bone formation measured with FMT and bone formation rate measured with in vivo micro-CT. Bone formation measured by FMT was 89-109% greater (p<0.05) for mice subjected to mechanical loading than control mice. Bone resorption was 5-8% lower, but did not reach a significant difference between groups, indicating moderate sensitivity for FMT. In conclusion, in vivo FMT in mouse tail bones is feasible but needs to be optimized for monitoring load adaptation in living mice.

A group social skills intervention program for survivors of childhood brain tumors.

OBJECTIVE: The purpose of this study was to evaluate the feasibility and preliminary outcomes of a social skills group intervention program for child brain tumor survivors. METHODS: Participants were 32 survivors (14 females) aged 8-18 years. Medulloblastoma (28%) was the main diagnosis. The intervention consisted of eight 2-hr weekly sessions focused on social skills including friendship making and assertion. Survivors and parents completed measures of social skills, quality of life, behavior and depression, at baseline, pre- and post-intervention, and 6 months later. RESULTS: Feasibility analyses revealed promising acceptability, retention, recruitment, and treatment fidelity. Significant improvement was found after intervention based on parents' reports of self-control [F(1,27) = 5.97, p <.05], social skills [F(1,28) = 5.70, p <.05], and quality of life [F(1,15) = 17.98, p <.01]. CONCLUSIONS: The intervention is feasible and outcomes based on parental reports provide preliminary support for the efficacy of the program.

Factors influencing depressive symptoms of children treated for a brain tumor.

OBJECTIVES: To examine depressive symptoms in children treated for a brain tumor and related clinical, demographic and personal factors. METHODS: Fifty-four children with brain tumors (32 males) aged 8.2-18.3 years participated. Standardized measures assessed depressive symptoms, social skills, self-worth and IQ. Clinical (treatment) and demographic variables (gender) were also examined. RESULTS: Depression scores were subjected to a 2 (gender), X 2 (social skills: low, high), X 3 (self-worth: low, average, high) ANCOVA with IQ as the covariate. Significant main effects of gender and of self-worth and an interaction between gender, social skills, and self-worth were observed. Gender was identified as a moderator of the effect of social skills and self-worth on depressive symptoms. CONCLUSIONS: Gender, social skills, and self-worth play important roles in the depressive symptoms of pediatric brain tumor patients.

The relationship between binge eating disorder and non-purging bulimia nervosa.

AIMS: To further investigate the differentiation between non-purging bulimia nervosa (BN-NP) and binge eating disorder (BED), particularly as concerns weight-shape overconcern affecting self-esteem, a core belief to both anorexia and bulimia nervosa. METHODS: Twenty-five female subjects with BN-NP and 25 female subjects with BED, consecutively referred to the Eating Disorder Unit of the DPPhNB, were administered the BEDCI, the EDI-2 and the BUT. RESULTS: BED patients had a higher BMI (35.5 vs. 23.8 kg/m2, p<0.0001) and were slightly older than BN-NP ones. Weight-shape concerns as one of the main/the most important things influencing self-esteem were reported by 68% of BN-NP patients and 62.5% of BED ones. Age at onset of binge-eating, weight-cycling, overall impairment due to the eating behavior, sexual harassment, depressive and substance abuse comorbidity were equally represented in the two groups of patients. BN-NP patients scored higher than BED ones as regards EDI drive for thinness (p<0.05) and BUT weight phobia (p<0.05), with these scores significantly related to differences in BMI (p<0.0005 and p=0.012). Weight-shape overconcern influencing self-esteem was predictive of an earlier onset of binge-eating (p<0.05) and higher scores at the BUT weight phobia, and body image concerns (p<0.05). CONCLUSIONS: Differences between BED and BN-NP seem to be more of degree than type and there seems little value in the separation between BED and BN-NP based on weight-shape concerns that substantially impair self-esteem. This construct seems core to both disorders and plays a substantial role in triggering and maintaining the binge-eating cycle.

Second-line treatment of advanced colorectal cancer with a weekly simultaneous 24-hour infusion of 5-fluorouracil and sodium-folinate: a multicentre phase II trial.

BACKGROUND: A weekly continuous 24-h infusion therapy with 5-fluorouracil (5-FU) preceded by a 2-h infusion of calcium folinate (CA-FA) was shown to be an effective first- and secondline treatment in advanced metastatic colorectal cancer. Substitution of CA-FA by the new formulation sodium folinate (S-FA) allows the simultaneous i.v. administration of folinic acid with 5-FU in one pump. PATIENTS AND METHODS: From 1999 to 2001, 42 patients with metastatic colorectal cancer after pre-treatment with a 5-FU bolus regimen were recruited in 5 centres to receive weekly 24-h infusions of 5-FU (2,600 mg/m2) and S-FA (500 mg/m2) dissolved in one pump for 6 weeks as second-line treatment. The treatment cycle was repeated after a 2-week rest period. RESULTS: 106 6-week cycles (median 2, range 1-6 per patient) were administered during the study. The median followup was 22 months. Out of 42 patients, 1 (2%) achieved complete remission, 3 (7%) partial remission, and 31 (74%) no change. Median time to tumour progression was 5.7 months (95% CI: 4.1-6.5). The median survival was reached at 14.7 months (95% CI: 11.0-22.0). Among major toxicities, NCI-CTC grade III/IV diarrhoea occurred in 8/42 (19%), grade III hand-foot-syndrome in 5/42 (12%) and grade III/IV stomatitis in 3/42 (7%) patients. CONCLUSION: Similar to conventional 24-h 5-FU + CA-FA treatment, the combination with S-FA in second-line therapy induced 9% objective responses and stopped tumour progression in 74%. The simultaneous administration of both, S-FA and 5-FU over 24 h dissolved in one pump is convenient, safe and effective as second-line treatment for patients with colorectal cancer.

Contribution of lymphatic drainage system in corneal allograft rejection in mice.

PURPOSE: To modulate aqueous outflow via the uveoscleral pathway and to determine its influence on corneal graft survival in mice. METHODS: BALB/c mice received corneal transplants from C3H mice and were placed randomly in three treatment groups: saline, pilocarpine or latanoprost. Three further groups received adjuvant systemic and topical corticosteroids. The kinetics of infiltrating lymphocytes, neutrophils and macrophages in the transplants was investigated in an additional 96 animals. Cytokine expression in the submandibular lymph nodes and spleen was investigated using in-situ hybridization and RNAse protection assay. Tracer experiments were conducted using 99mTC colloidal albumin Nanocoll; count rates were determined in the submandibular lymph nodes, spleen and blood following both subconjunctival and intracameral injection. RESULTS: Neither pilocarpine nor latanoprost had any influence on aqueous outflow or allograft survival in mice. Neutrophils and macrophages dominated the infiltrating cells 11 days postoperative in both treated and untreated grafts. On postoperative day 13, a greater increase in lymphocytes than in other cell groups was observed in allogeneic grafts. Following allogeneic transplantation, 1% of lymphocytes in ipsilateral submandibular lymph nodes were positive for IFN-gamma. Tracer studies revealed a 16% aqueous outflow via the uveoscleral routes following intracameral injection of Nanocoll; this was increased by 97% with subconjunctival injection. CONCLUSION: Our data confirm the existence of functional lymphatic drainage via the uveoscleral pathway and conjunctiva in the mouse. Cells within the ipsilateral submandibular lymph node respond to stimuli upstream. This reaction could potentially be manipulated to improve graft survival.

The effect of corticosteroid and cyclosporin A on murine corneal allograft rejection.

BACKGROUND: The immunomodulatory T-helper type 1 (Th1) cytokine interferon-gamma (IFN-gamma) was measured in serum and cornea to ascertain its general contribution to corneal graft rejection and to establish a rational basis for the decision for or against systemic therapy. METHODS: Eight groups of differently treated BALB/c (H-2d) mice received a C3H (H-2 k) corneal graft. There was one saline-treated control group and two groups that received intramuscular cyclosporin A (CsA) for 14 or 40. Three groups received systemic or topical, systemic plus topical corticosteroid treatment, which was combined with CsA in two further groups. To measure the IFN-gamma level by enzyme-linked immunosorbent assay (ELISA), blood was taken by heart puncture and corneae were excised at the limbus. RESULTS: Five days of systemic corticosteroid and 14 days of CsA had no significant effect on graft survival. A 40-day CsA treatment and a 40-day combined corticosteroid treatment significantly prolonged graft survival. An 80-day topical corticosteroid treatment produced additional prolongation. IFN-gamma could not be detected (limit of detection 25 pg/ml) in any of the serum samples, while significantly increased amounts of IFN-gamma were detected in the supernatants of the corneal tissue 13 or 14 days after allogeneic but not syngeneic corneal graft, corresponding to 9.5 pg, 5.1 pg and 1.8 pg per cornea. CONCLUSION: The detection of Th1 cytokines in the cornea but not the serum of mice at the time of allograft rejection is in accordance with the finding of long-lasting dose-dependent immunosuppression of topical steroids and the inefficacy of short-term systemic CsA and corticosteroids.

The HTR1 gene is a dominant negative mutant allele of MTH1 and blocks Snf3- and Rgt2-dependent glucose signaling in yeast.

Saccharomyces cerevisiae HTR1 mutants are severely impaired in the uptake of glucose. We have cloned dominant HTR1 mutant alleles and show that they encode mutant forms of the Mth1 protein. Mth1 is shown to be involved in carbon source-dependent regulation of its own, invertase and hexose transporter gene expression. The mutant forms block the transduction of the Snf3- and Rgt2-mediated glucose signals upstream of the Rgt1 transcriptional regulator.

Characterization of a glucose-repressed pyruvate kinase (Pyk2p) in Saccharomyces cerevisiae that is catalytically insensitive to fructose-1,6-bisphosphate.

We have characterized the gene YOR347c of Saccharomyces cerevisiae and shown that it encodes a second functional pyruvate kinase isoenzyme, Pyk2p. Overexpression of the YOR347c/PYK2 gene on a multicopy vector restored growth on glucose of a yeast pyruvate kinase 1 (pyk1) mutant strain and could completely substitute for the PYK1-encoded enzymatic activity. PYK2 gene expression is subject to glucose repression. A pyk2 deletion mutant had no obvious growth phenotypes under various conditions, but the growth defects of a pyk1 pyk2 double-deletion strain were even more pronounced than those of a pyk1 single-mutation strain. Pyk2p is active without fructose-1,6-bisphosphate. However, overexpression of PYK2 during growth on ethanol did not cause any of the deleterious effects expected from a futile cycling between pyruvate and phosphoenolpyruvate. The results indicate that the PYK2-encoded pyruvate kinase may be used under conditions of very low glycolytic flux.

Intracranial germ-cell tumours--treatment results and residuals.

UNLABELLED: There is only sparse information about the development of children after successful treatment for intracranial germ-cell tumours. Between January 1981 and June 1992, 26 children with intracranial germ-cell tumours were treated in the University Hospital Hamburg-Eppendorf. We report on treatment results, long standing residuals and the "quality of life" of these patients. The long-term event-free survival was 88% for the germinomas and 43% for the malignant teratomas. Of the patients 58% had no relevant functional neurological deficits and 37% had mild impairment. Only 1 patient with metastatic disease was severely handicapped. Six patients showed neuro-endocrine dysfunction. All of them had suprasellar/hypothalamic lesions and all received successful substitution therapy. As to neuropsychological functions, 53% of the patients had no or only mild disturbances. The most affected function was speed of information processing. Of the children 69% were able to proceed with their education at the same level as before therapy. The overall self-assessment revealed good results in 75% of the patients. CONCLUSION: After surgical removal and radiation therapy long-term survival of intracranial germinomas amounts to 88%. Despite craniospinal axis radiation severe residuals are rare and a good quality of life is common. In malignant teratomas treatment regimens including chemotherapy are much less successful.

Development of a regional cohort of very-low-birthweight children at six years: cognitive abilities are associated with neurological disability and social background.

The authors studied the intelligence, memory, visuomotor skills and la nguage of 298 six-year-old children with very low birthweight (VLBW) (less that 1500g). Of 591 VLBW childern born July 1983 to June 1986 within 50km of the centre of Hamburg, Germany, 330 were traceable at age six years and 298 of these were seen by a neuropaediatrician and a psychologist; the other 19 were too severely disabled for psychological assessment with the standardized tests used. The mean memory performance of VLBW children at age six years was below the standard mean in all diagnostic and socio-economic subgroups. As expected, visuomotor development was clearly influenced by neurological but not socio-economic status. Intelligence and language skills were much more closely related to socio-economic background that to neurological morbidity. However, VLBW children with hyperactivity, clumsiness or cerebral palsy differed significantly in intelligence and visuomotor performance from those without neurological symptoms.

[Tumors of the cerebral hemispheres in children and adolescents. Results of treatment, residual syndromes and focal epilepsy]. / Grosshirnhemisphärentumoren bei Kindern und Jugendlichen. Behandlungsergebnisse, Residualsyndrome und fokale Epilepsien.

Tumors of the cerebral hemispheres comprise a big variety of histologic tumor types. Therefore, in the literature usually only specific subgroups such as benign gliomas and temporal lobe tumors are reported. In this study we report on 44 tumors of the cerebral hemispheres, including 9 angiomas. Apart from the treatment results concerning event free survival, the neurological and neuropsychological outcome of the patients were assessed. A peculiarity in the hemispheric tumors is their association with focal epilepsies. In 94% of our patient series, epileptic seizures had been the first tumor associated symptom and approximately 62% developed focal epilepsy. Seizure types, their association with tumor location and histology, the success of tumor therapy in concern of the epilepsy and the significance of the electroencephalogram in the follow up care of these patients were assessed separately.

Malignant melanotic neuroectodermal tumor of infancy.

A 2-month-old boy underwent surgery for removal of a right temporal melanotic neuroectodermal tumor of infancy (MNTI). Histologically the tumor tissue showed signs of malignancy. The child was reexamined several times up to the age of 5 years. Neuroradiological evaluation showed no evidence of tumor recurrence or metastases. No resulting handicap was observed during neurological and psychological follow-up examination at the age of 5 years. Our findings confirm that surgical removal as the therapy of choice provides an excellent prognosis for this kind of tumor in spite of its histologically malignant appearance.