Renal size and function after cure of Wilms' tumour.

Now that most patients with Wilms' tumour are cured, it is practicable to study the long-term morbidity of their treatment and use this information to reduce treatment sequelae in the future. In this study we evaluate the size and function of the remaining kidney in 53 survivors of Wilms' tumour with a mean off treatment follow-up of 13 years. There was evidence of renal dysfunction in 17 (32%), including ten (19%) with a low GFR (< 80 ml/min/1.73 m2SA), six (11%) with hypertension and five (9%) with increased urinary albumin excretion. Measurements of renal size showed 'good' renal compensatory hypertrophy in only 55% of patients. 'Good' refers to renal size of more than 2 s.d. above the mean renal length for children with two kidneys. There were no correlations between GFR, renal size, blood pressure, microalbuminuria or type of treatment. However, children less than 24 months at diagnosis and children receiving chemotherapy with radiation doses to remaining kidney of more than 1200 cGy had a worse renal prognosis. Patients whose Wilms' tumour is diagnosed in infancy should have careful long-term follow-up of renal function and size. Older patients may safely be followed up less often, unless their remaining kidney was received > 1200 cGy.     

Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

Investigation of three new mouse mammary tumor cell lines as models for transforming growth factor (TGF)-β and Neu pathway signaling studies: identification of a novel model for TGF-β-induced epithelial-to-mesenchymal transition

Introduction  

This report describes the isolation and characterization of three new murine mammary epithelial cell lines derived from mammary tumors from MMTV (mouse mammary tumor virus)/activated Neu + TβRII-AS (transforming growth factor [TGF]-β type II receptor antisense RNA) bigenic mice (BRI-JM01 and BRI-JM05 cell lines) and MMTV/activated Neu transgenic mice (BRI-JM04 cell line).     

Response to influenza virus vaccination in vertical HIV infection

OBJECTIVE: To assess the antibody response to influenza vaccine of children vertically infected with HIV. DESIGN: Prospective study in HIV infected children vaccinated during the winter of 1994-5. SETTING: Family HIV clinic at St Mary's Hospital, Paddington. SUBJECTS: 25 children, aged 1-11 years, vertically infected with HIV. MAIN OUTCOME MEASURES: Responses to influenza antigens (H1N1-A/Taiwan/1/86, H3N2-A/Shandong/9/93, B/Panama/45/ 90) were tested by haemagglutination inhibition. Antibody responses were assessed according to clinical symptoms and immune function, stratified according to the 1994 revised classification for HIV infection in children. RESULTS: 23 children (92%) had either very low or no detectable antibody before vaccination. New protective antibody responses were made by 10 children (40%): in seven to a single antigen, in two to two antigens, and in one to all three antigens. For each antigen there was an overall small increase in the mean geometric titre of antibody produced, but this only reached a protective level for antigen H1N1 and for children with minimal symptoms. Less symptomatic children were significantly more likely to produce a protective antibody response to influenza vaccination. No association was found between immune function, as measured by CD4 count, and vaccine response. CONCLUSIONS: Only vaccination of the least symptomatic HIV infected children against influenza is likely to be effective. This will not only protect them against influenza, but will also protect other more immunosuppressed and vulnerable members of their families.     

Involving children and young people in clinical research through the forum of a European Young Persons’ Advisory Group: needs and challenges

Children and young people are seen as fundamental to the design and delivery of clinical research as active and reflective participants. In Europe, involvement of children and young people in clinical research is promoted extensively in order to engage young people in research as partners and to give them a voice to raise their own issues or opinions and for their involvement in planning and decision making in addition to learning research skills. Children and young people can be trained in clinical research through participation in young person advisory groups (YPAGs). Members of YPAGs assist other children and young people to learn about clinical research and share their experience and point of view with researchers, thereby possibly influencing all phases of research including the development and prioritization of research questions, design and methods, recruitment plans, and strategies for results dissemination. In the long term, the expansion of YPAGs in Europe will serve as a driving force for refining pediatric clinical research. It will help in a better definition of research projects according to the patients’ needs. Furthermore, direct engagement of children and young people in research will be favorable to both researchers and young people.     

In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia

Recent reports have established the prenatal origin of leukemia translocations and resultant fusion genes in some patients, including MLL-AF4 translocations in infants and TEL-AML1 translocations in children. We now report evidence for the prenatal origin of a translocation in childhood acute myeloid leukemia (AML). The t(8;21) AML1-ETO translocations were sequenced at the genomic level in 10 diagnostic leukemia samples from children with available neonatal Guthrie blood spots. Clonotypic genomic AML1-ETO sequences were detected in the Guthrie spots for 5 individuals, providing unambiguous evidence of prenatal origin in these cases. Two of these patients were older than 10 years of age at diagnosis, indicative of a protracted postnatal latency. Three of the patients were assessed for the persistence of genomic fusion sequences in complete clinical remission samples and were found to be positive. These data indicate that t(8;21) in childhood AML can arise in utero, possibly as an initiating event in childhood AML, and may establish a long-lived or stable parental clone that requires additional secondary genetic alterations to cause leukemia.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Consulting the community: public expectations and attitudes about genetics research

Genomic discoveries and technologies promise numerous opportunities for improving health. Key to these potential health improvements, however, are health-care consumers'' understanding and acceptance of these new developments. We identified community groups and invited them to a public information-consultation session in order to explore public awareness, perception and expectations about genetics and genomics research. One hundred and four members of seven community groups in Newfoundland, Canada took part in the community sessions. Content analysis of participant comments revealed they were largely hopeful about genetics research in its capacity to improve health; however, they did not accept such research uncritically. Complex issues arose during the community consultations, including the place of genetics in primary care, the value of genetics for personal health, and concerns about access to and uses of genetic information. Participants unequivocally endorsed the value of public engagement with these issues. The rapid pace of discoveries in genomics research offers exciting opportunities to improve population health. However, public support will be crucial to realize health improvements. Our findings suggest that regular, transparent dialog between researchers and the public could allow a greater understanding of the research process, as well as assist in the design of efficient and effective genetic health services, informed by the public that will use them.