Parenting children with intellectual disability: linking maternal insightfulness to sensitivity.

BACKGROUND: This study examined mothers' representation of their children's inner world - maternal insightfulness - and its link to sensitive maternal behaviour. We aimed to understand some of the parental processes that underlie parenting children with intellectual disability (ID). METHODS: The sample included 38 mothers and their children with non-specific ID aged 2.5 to 5.5 years. Children had developmental quotient scores of M = 56.29, SD = 9.65 and adaptive behaviour scores of M = 60.72, SD = 10.43. We hypothesised that mothers who were insightful show more sensitive behaviour when interacting with their children than non-insightful mothers do. Maternal insightfulness was assessed using the insightfulness interview, and maternal sensitive behaviour during mother-child interaction was assessed using the emotional availability observation scales. RESULTS: Forty-one per cent of the mothers showed positive insightfulness regarding their children's inner world. These mothers showed higher levels of sensitive behaviour than did the non-insightful mothers. The insightfulness-sensitivity link was not associated with any of the mothers' or the children's characteristics, including the level of developmental quotient, suggesting that these parental constructs are not simply a reflection of the level of the children's developmental delay. CONCLUSIONS: Better understanding of the mechanism of parenthood, including the insightfulness-sensitivity link, may help personalise the support provided to parents of children with ID. The associations between maternal insightfulness and sensitivity imply that promoting maternal insightfulness may enhance mothers' sensitivity towards their children.

An exploratory, open-label, randomized, multicenter study to investigate the pharmacodynamics of a glycoengineered antibody (imgatuzumab) and cetuximab in patients with operable head and neck squamous cell carcinoma.

BACKGROUND: In addition to inhibiting epidermal growth factor receptor (EGFR) signaling, anti-EGFR antibodies of the IgG1 'subtype' can induce a complementary therapeutic effect through the induction of antibody-dependent cell-mediated cytotoxicity (ADCC). Glycoengineering of therapeutic antibodies increases the affinity for the Fc-gamma receptor, thereby enhancing ADCC. PATIENTS AND METHODS: We investigated the changes in immune effector cells and EGFR pathway biomarkers in 44 patients with operable, advanced stage head and neck squamous cell carcinoma treated with two preoperative doses of either glycoengineered imgatuzumab (GA201; 700 or 1400 mg) or cetuximab (standard dosing) in a neoadjuvant setting with paired pre- and post-treatment tumor biopsies. RESULTS: Significant antitumor activity was observed with both antibodies after just two infusions. Metabolic responses were seen in 23 (59.0%) patients overall. One imgatuzumab-treated patient (700 mg) achieved a 'pathological' complete response. An immediate and sustained decrease in peripheral natural killer cells was consistently observed with the first imgatuzumab infusion but not with cetuximab. The functionality of the remaining peripheral natural killer cells was maintained. Similarly, a pronounced increase in circulating cytokines was seen following the first infusion of imgatuzumab but not cetuximab. Overall, tumor-infiltrating CD3+ cell counts increased following treatment with both antibodies. A significant increase from baseline in CD3+/perforin+ cytotoxic T cells occurred only in the 700-mg imgatuzumab group (median 95% increase, P < 0.05). The most prominent decrease of EGFR-expressing cells was recorded after treatment with imgatuzumab (700 mg, -34.6%; 1400 mg, -41.8%). The post-treatment inflammatory tumor microenvironment was strongly related to baseline tumor-infiltrating immune cell density, and baseline levels of EGFR and pERK in tumor cells most strongly predicted therapeutic response. CONCLUSIONS: These pharmacodynamic observations and relationship with efficacy are consistent with the proposed mode of action of imgatuzumab combining efficient EGFR pathway inhibition with ADCC-related immune antitumor effects. CLINICAL TRIAL REGISTRATION NUMBER: NCT01046266 (ClinicalTrials.gov).

Glyco-engineered anti-EGFR mAb elicits ADCC by NK cells from colorectal cancer patients irrespective of chemotherapy.

BACKGROUND: The epidermal growth factor receptor (EGFR) is overexpressed in colorectal cancer (CRC), and is correlated with poor prognosis, making it an attractive target for monoclonal antibody (mAb) therapy. A component of the therapeutic efficacy of IgG1 mAbs is their stimulation of antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells bearing the CD16 receptor. As NK cells are functionally impaired in cancer patients and may be further compromised upon chemotherapy, it is crucial to assess whether immunotherapeutic strategies aimed at further enhancing ADCC are viable. METHODS: CRC patients before, during and after chemotherapy were immunophenotyped by flow cytometry for major white blood cell populations. ADCC-independent NK cell functionality was assessed in cytotoxicity assays against K562 cells. ADCC-dependent killing of EGFR(+) A431 cancer cells by NK cells was measured with a degranulation assay where ADCC was induced by GA201, an anti-EGFR mAb glyco-engineered to enhance ADCC. RESULTS: Here, we confirm the observation that NK cells in cancer patients are dysfunctional. However, GA201 was able to induce robust NK cell-dependent cytotoxicity in CRC patient NK cells, effectively overcoming their impairment. CONCLUSIONS: These findings support the evaluation of the therapeutic potential of GA201 in combination with chemotherapy in CRC patients.

[Childhood cerebral tumors: morbidity and follow-up into adulthood]. / Tumeurs cérébrales de l'enfant: morbidité et suivi à l'âge adulte.

This chapter presents guidelines for the follow-up of children with brain tumors, whether benign or malignant, in their transition to adulthood. The consequences of their disease and its treatment overlap greatly. The complications and long-term follow-up are detailed based on the specialists involved.

A writing workshop for children with cancer.

We present and comment on several short texts written in a writing workshop by children and adolescents treated for cancer. In addition to the obvious themes, the patients communicate the intense elements of the experience they are going through, including fear of injections, fear of not being cured, revolt, hope and a feeling of unreality, and raise the question "Why?". They are proud to express their feelings, thoughts and creativity, and relieved to be able show that they remain themselves. This can help them maintain or regain confidence in themselves and in the ability of their parents and medical staff to understand them. We consider their pleasure, their parents' and caregivers' reactions and the quality of their work as it relates to their age, academic level, cultural environment and cognitive capacities. These examples may help to inform physicians and nurses about how they perceive patients (children or adults) and their needs and abilities, and thereby improve the quality of the relationship.

[A multidisciplinary consultation for children with brain tumors]. / Une consultation multidisciplinaire pour les enfants traités pour une tumeur cérébrale.

UNLABELLED: School achievement of children with brain tumors is hampered by progressive neurologic and cognitive sequelae. To help the children and their family, we have created in 1997 a multidisciplinary consultation together with Necker's hospital. MATERIAL AND METHODS: The study describes the organization of the consultation and analyses the files of 69 children seen between September 2001 and June 2002. RESULTS AND CONCLUSION: The authors conclude that this consultation is an irreplaceable mean to coordinate the complex rehabilitation process of a child treated for a brain tumor.

Ethical issues in pediatric oncology phase I-II trials based on a mother's point of view.

Phase I-II trials are developing in Pediatrics and raise many complex relational, psychological and ethical issues. We present and discuss these based on an interview in a pediatric oncology setting, with a mother who accepted that her daughter be included in such trials and who expressed why she accepted with great sensitivity and profoundness. She explained that after many years of inefficient treatments she had lost all her landmarks and was ready to accept any proposition, even those she would have considered unacceptable earlier. She did not know whether there is a limit to what is acceptable. Her only objective was to gain any time possible in order to continue living with her daughter. She found it important that the research doctor be different from the doctor involved in patient care, and that the latter remains the major decision-maker and correspondent: thus the child's best interests take precedence over that of research. Interviews with the psycho-oncologist can help the parents and the doctors gain a better insight into the various aspects, rational and irrational, conscious and unconscious, involved in the proposition to participate in a clinical trial and in the parents' or the child's acceptance or refusal.

[Adolescents treated for cancer and fertility preservation. Psychological aspects]. / Les adolescents traités pour un cancer et la préservation de leur fertilité. Aspects psychologiques.

Sperm preservation should be proposed to all the adolescents undergoing treatment for a cancer, because fertility is a major desire of young adults cured of a cancer. Proposing sperm preservation is among the oncologist's concerns about preventing sequels. However, this proposition can give rise to psychological problems as it concerns cancer and adolescence. For sperm collection to take place in a favourable climate with the adolescent's approval, their psychology and behaviour towards cancer should be well apprehended: they worry about their body, their appearance, their sexuality, their relations with their peers and their parents, their value, their narcissism, and their identity; but they can also be anxious, pessimistic about their future, disillusioned with parenthood, afraid of transmitting cancer, etc. Knowing these aspects helps one to understand and overcome any reluctance and to attenuate feelings of guilt and suffering in case of failure. Thus, a balance can be struck between overrespecting superficial opposition and imposing a decision that is not authentically theirs. In addition, closer relations nurtured between the sperm bank and oncohaematology departments, adolescent-friendly information material, and a better knowledge of adolescent psychology could also be helpful.

Testing a Rapid Diagnostic Medium for Erwinia amylovora and Development of a Procedure for Sampling Blossoms in Pear Orchards.

ABSTRACT The coliform agar produced by Merck was tested for rapid diagnosis of Erwinia amylovora (the causal agent of fire blight) in pear blossoms. The medium enabled the diagnosis to be completed within 36 h. Diagnoses performed with the medium were confirmed by the BIOLOG and the fatty-acid profile methods. The diagnostic medium was used to determine the spatial distribution of colonized blossoms in the orchards and it was found that E. amylovora may be distributed both in clusters and at random. These findings were used in the development of a statistical model for sampling blossoms in the orchard. The model determines the number of trees to be sampled in the orchard and the number of blossoms be taken from each tree, which would enable the true colonization incidence of blossoms in the orchard to be estimated at desired levels of accuracy and confidence. Parameters included in the model are: the total number of trees in the orchard (T), the number of trees to be sampled in the orchard (t), the number of blossoms to be sampled from each tree (n), the true colonization incidence of blossoms (pi), a coefficient of aggregation (rho), the required level of confidence (1 - alpha), and the required level of accuracy (L). Sensitivity analyses revealed that the parameter governing sample size is the required level of accuracy. Sampling of 20 blossoms from each of several hundred trees is required to achieve an accuracy of +/-1%, but only a few single trees are needed for an accuracy level of +/-10%. A sampling procedure then was developed, validated with an independent data set, and found to be accurate. It was concluded that sampling of pear blossoms and estimation of the incidence of blossom colonization by E. amylovora could improve fire blight management, but not in all cases.

Evaluation of local and imported fire blight warning systems in Israel.

ABSTRACT The possibility of using local and imported warning systems for the management of fire blight (caused by the bacterium Erwinia amylovora) in pears was tested in Israel from 1997 to 2000. Three imported systems (MARYBLYT 4.3, BIS95, and Cougarblight 98C) and one local system (Fire Blight Control Advisory [FBCA]) were used. All systems were tested in simulation experiments; MARYBLYT 4.3 and FBCA were also tested in orchard experiments under natural infections. Simulation experiments included 193 orchard-plots in which the time of disease onset enabled us to determine the date of infection. Thirty-five experiments were conducted in commercial orchards; in 10 of these, fire blight developed naturally. The performance of the imported warning systems was too variable to be accurately used under Israeli conditions. In the simulation experiments, the success rate (i.e., the capacity of the systems to predict the exact date of the occurrence of infection episodes) of the imported systems was low (3 to 55%) with considerably large variability among years (CV = 30 to 67%). Similar results were obtained in the orchard experiments for MARYBLYT 4.3: in only two of five experiments where plots were managed according to that system was disease severity significantly lower than that recorded in untreated control plots. In comparison, the local system, FBCA, predicted most infection episodes in the simulation experiments with low variability (99%, CV = 1.0%). In the orchard experiments, adequate disease suppression was achieved in all eight experiments in which FBCA recommendations were followed. We concluded that it was not possible to import and successfully implement fire blight warning systems in Israel that have been developed in regions with dissimilar environmental conditions.

New Considerations for Pruning in Management of Fire Blight in Pears.

The efficacy of pruning infected pear tissues to combat fire blight (caused by Erwinia amylovora) was evaluated in two sets of experiments conducted during 1999 to 2001 in Israel. In the first set of two experiments, diseased tissues were removed soon after the observation of blossom infections. Pruning was effective in 0 to 50% of the treated trees, and resulted in complete eradication of E. amylovora. In the remaining trees, pruning not only did not result in eradication of the bacteria from the tree tissues, it made the situation worse, as the disease had invaded the main branches and limbs of a significantly larger proportion of pruned trees than of non-pruned ones, because of alteration of the physiological status of the host plant by pruning. In the five experiments of the second set, the efficacy of pruning fire blight infections on main branches and limbs was studied; the time of pruning varied among the experiments. Effectiveness of cutting and removing infected branches and limbs was linearly related to time of treatment: the efficacy of pruning improved significantly with lateness of the treatment. The best results were obtained when pruning was carried out while the trees were dormant, in December: none of these trees had a severely infected canopy the following spring. Based on the results obtained in this study, it was concluded that factors related to all three components of the disease triangle (i.e., pathogen, host, and environment), rather than only the actual presence of diseased tissues, should be taken into account in considering the need for cutting and removing fire blight-diseased tissues. Accordingly, recommendations for Israeli growers were revised and updated.

The Role of Autumn Infections in the Progression of Fire Blight Symptoms in Perennial Pear Branches.

The role of autumn infections in the progression of fire blight (caused by Erwinia amylovora) symptoms in perennial pear branches was studied in orchard-grown trees in Israel. The extent of symptom progression and the final length of fire blight cankers in perennial branches were variably affected by the vigor of the trees and the season of infection. Following spring infections, when all trees supported active shoot growth, fire blight symptoms progressed more rapidly and to longer distances in trees that exhibited high vigor (i.e., with numerous annual shoots on most terminal branches) than in low-vigor trees (i.e., few or no annual shoots on terminal branches). Irrespective of the vigor of the trees, the progression of fire blight symptoms in perennial branches ceased between mid-May and mid-July, and only a small proportion (0 to 14.2%) of the infections had invaded main limbs or trunks of trees. Progression of fire blight symptoms following autumn infections was related to the preceding summer (August to No-vember) shoot regrowth: in trees in which the shoots did not restore their growth in the summer, the rate of symptom progression in perennial branches was higher in trees with a low vigor than in those with a high vigor, whereas for those with summer regrowth the relationship between rates of symptom expression was reversed. Irrespective of the vigor group and of whether there was summer regrowth, symptoms in perennial branches continued to progress through the winter until the following spring. Most of the autumn infections (50 to 78.5%) that developed in susceptible trees had invaded main limbs or trunks of trees. The results of this study indicate that factors related to host phenology and physiology, rather than factors related to environmental influences (such as temperature), govern the extent, rate, and duration of fire blight progression in perennial pear branches. Furthermore, it turned out that autumn infections play a substantial role in fire blight epidemiology in Israel.

Changes in the Sensitivity of Erwinia amylovora Populations to Streptomycin and Oxolinic Acid in Israel.

A survey of streptomycin resistance in the fire blight pathogen, Erwinia amylovora, conducted in pear, apple, and quince orchards in Israel during 1998 to 2001 revealed a decrease in the frequency of locations with streptomycin-resistant strains, from 57% in 1998 to 15% in 2001. In 2001, streptomycin-resistant strains were detected in only five locations in two restricted areas in western Galilee and the Golan Heights, compared with 16 locations found in 1998 throughout the northern part of the country. Since the use of streptomycin for fire blight control was terminated in 1997, this antibiotic has been replaced with oxolinic acid (Starner) in commercial orchards. Strains resistant to oxolinic acid were isolated from two pear orchards in the northern part of Israel in 1999. In a nationwide survey conducted during the spring and winter of 2000 and 2001, 51 and 47 pome fruit orchards, respectively, were sampled. Oxolinic acid-resistant strains were detected in several orchards located in two restricted areas in northern Galilee. Strains with resistance to both streptomycin and oxolinic acid were not found during 2000 to 2001. Results of this survey are used in managing fire blight with bactericides.

How do parents perceive high-dose chemotherapy and autologous stem cell transplantation for their children.

Our objective was to understand the parents' perception of children treated in an ASCT unit. Parents (40) of children and adolescents were interviewed by the department psychiatrist-psychoanalyst, over 9 months. They expressed great distress (22), considerable difficulty in assuming their parental role (with feelings of helplessness and guilt), and had distorted relations with the child whose behavior was unusual and incomprehensible (22). The relation with care providers, who should be 'all-powerful' and harmless, was ambivalent (15). They found it difficult to think or refused to do so, because their 'thoughts are terrifying', and they wanted to forget everything (11). The couple was going through a crisis (9). Temporal landmarks were disturbed (8); ASCT was experienced as a threatening discontinuity in the course of treatment (parents were unable to think of the past, the future, or the present); social landmarks were disturbed (6) with loss of social and professional relations. We concluded that parents may experience intense distress and disorientation. Trained to understand the parents' and their children's thoughts and behavior, the medical team, which includes a psycho-oncologist, can better help them to understand and support the children, to strike a balance between their parental role and other responsibilities, and prevent conflicts.

Regulation of cutaneous malignancy by gammadelta T cells.

The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.

[Li-Fraumeni syndrome: update, new data and guidelines for clinical management]. / Le syndrome de Li-Fraumeni: mise au point, données nouvelles et recommandations pour la prise en charge.

The Li-Fraumeni syndrome (LFS) is an inherited form of cancer, affecting children and young adults, and characterized by a wide spectrum of tumors, including soft-tissue and bone sarcomas, brain tumours, adenocortical tumours and premenopausal breast cancers. In most of the families, LFS results from germline mutations of the tumor suppressor TP53 gene encoding a transcriptional factor able to regulate cell cycle and apoptosis when DNA damage occurs. Recently, germline mutations of hCHK2 encoding a kinase, regulating cell cycle via Cdc25C and TP53, were identified in affected families. The LFS working group recommendations are the following: (i) positive testing (screening for a germline TP53 mutation in a patient with a tumor) can be offered both to children and adults in the context of genetic counseling associated to psychological support, to confirm the diagnosis of LFS on a molecular basis. This will allow to offer to the patient a regular clinical review in order to avoid a delay to the diagnosis of another tumor; (ii) the 3 indications for positive testing are: a proband with a tumor belonging to the narrow LFS spectrum and developed before age 36 and, at least, first- or second-degree relative with a LFS spectrum tumor, before age 46, or a patient with multiple primary tumors, 2 of which belonging to the narrow LFS spectrum, the first being developed before 36 or a child with an adenocortical tumour; (iii) presymptomatic testing must be restricted to adults; (iv) the young age of onset of the LFS tumors the prognosis of some tumors, the impossibility to ensure an efficient early detection and the risk for mutation carriers to develop multiple primary tumors justify that prenatal diagnosis might be considered in affected families.

[Parents' opinions of pediatric oncology day hospitals]. / Comment les parents apprécient-ils un hôpital de jour en oncologie pédiatrique.

AIM: The aim of this study was to assess parental opinions on the advantages and disadvantages of a pediatric oncology day hospital (DH) so that the structure can be better adapted to the children's needs and parents' expectations, and provide a potentially valid alternative to conventional hospitalization (CH). METHODS: Over a 15-days period, 39 parents of children treated at a DH were approached and asked to fill in a questionnaire on their opinion of the advantages and disadvantages of a DH compared to a CH. RESULTS: The results of this survey were significant. The majority of parents preferred the DH to the CH (69% versus 15%). The illness was perceived as being less severe; and as the child was not continually in the CH context, he/she was able to forget the illness and the hospital to some extent, and was therefore not as anxious. The DH appeared to be better adapted to the child's needs and facilitated the pursuit of normal family life and everyday activities, but imposed constraints on social and professional activities. On the other hand, the CH provided a reassuring treatment context including more comprehensive information, and in particular a better integration of the child and careful monitoring of the disease within the oncology department, and closer relations between the different parents visiting the hospital. In spite of the high preference rate for the DH, in some instances certain disadvantages could outweigh the advantages, e.g., fatigue due to journeys to and from the hospital, or living too far away from the DH; a lack of punctuality, which meant that the parents were unable to plan their day with any certainty; insufficient comfort (noise, a limited number of rooms available); inadequate information; a lack of privacy; and the anxiety connected with having to assume too much responsibility. CONCLUSION: Overall, it was concluded that the parents appeared to appreciate the aims of the DH (i.e., limiting the treatment constraints imposed on the patient and on the parents themselves, thereby maintaining the quality of family life, assuring adequate treatment, reducing cost of treatment). However, the authors consider that the DH has to be organized in such a way that it takes into account the following: the social aspects, i.e., living conditions, parents' social, economic and professional status; parents' and children's psychological traits, expectations; and access to a local care system. The DH should also have sufficient means and staff at its disposal. Without taking these factors into consideration, the DH and other alternatives to the CH will not be able to adequately care for the patients, or meet the parents' expectations, and may even have a negative effect on the family.

Guidelines for the recognition, prevention, and remediation of burnout in health care professionals participating in the care of children with cancer: report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.

This is the eighth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, instituted in 1991. It deals with a topic discussed and approved by the SIOP Committee; namely, "Recognition, prevention, and remediation of burnout in health care professionals participating in the care of children with cancer." It is addressed to the Pediatric Oncology community and outlines: 1) the general definition of burnout as mental and physical exhaustion, indifference, sense of failure as a professional, and sense of failure as a person; 2) the causes of burnout from the nature of the work itself, the work environment, and the characteristics of the individual; 3) the prevention of burnout, changing the detrimental aspects of one's work environment and modifying one's own behavior; and accepting methods to remediate burnout when it occurs.

Psychotherapeutic practice in paediatric oncology: four examples.

Psychotherapy, often used with children treated for a solid tumour, is seldom described. We present four examples of such therapies: a mother who refused enucleation for her 7-month-old boy; a boy's jealousy towards his sister who was being treated for a brain tumour; a teenager troubled by his scar; a 7-year-old boy embarrassed by the unconscious memory of his treatment when he was 5 months old. All names have been changed, for reasons of privacy. Psychotherapies aim to help children and parents to cope with the violent experience of having cancer, to recover their freedom of thought and decision-making concerning their life, their place in the family, their body image, their self-esteem, their identity. These descriptions of brief psychotherapy could help paediatricians to gain a more thorough understanding of the child's experience, to improve collaboration with psychotherapists and to confront clinical skills of psychotherapists.