(18)F-FDG-PET/CT in evaluating response to therapy in solid tumors: where we are and where we can go.

In the past, enormous public and private investments have been made to reduce cancer incidence and mortality. Despite some improvements over the last 10 years, the overall outcome of the "war on cancer" has been disappointing. Among the reasons for this limited success is our inability to determine, whether the therapeutic target is present, and whether the target is reached by the drug. A further important issue is our limited ability to correctly assess response to treatment early after start of therapy which would allow for more individualized treatment approaches. PET and PET/CT with the glucose analogue 2'-[(18)F]-fluoro-2'-deoxy-D-glucose (FDG) are increasingly used to assess response to therapy in patients, and a converging large body of evidence is emerging that suggests that changes in glucose utilization during therapy can be used to predict clinical outcome. In this article we provide an overview of the utility of (18)F-FDG PET/CT imaging for early monitoring of cancer therapy and address current and future challenges for its more widespread adoption. First, we discuss general requirements that any imaging modality must meet to provide valid and valuable treatment response assessment. We will then review the strengths and limitations of CT (RECIST) and PET based response criteria. Finally, we will examine the role of FDG-PET/(CT) imaging for response assessments in solid tumors.

[Enuresis in childhood]. / Serie Kindersprechstunde, Teil 2: Enuresis. "Mein Kind ist Bettnässer"!

In children with nocturnal bedwetting, the basic diagnostic evaluation to differentiate between monosymptomatic enuresis and organic or functional urinary incontinence is mandatory. When the diagnosis of monosymptomatic enuresis is set, a stepped therapeutic program is available, in which alarm/behavior therapy has a central role. Drug therapy of monosymptomatic enuresis in childhood is an established option and is reserved for certain indications.

Allergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle--the PARSIFAL study.

BACKGROUND: The prevalence of allergic diseases has increased rapidly in recent decades, particularly in children. For adequate prevention it is important not only to identify risk factors, but also possible protective factors. The aim of this study was to compare the prevalence of allergic diseases and sensitization between farm children, children in anthroposophic families, and reference children, with the aim to identify factors that may protect against allergic disease. METHODS: The study was of cross-sectional design and included 14,893 children, aged 5-13 years, from farm families, anthroposophic families (recruited from Steiner schools) and reference children in Austria, Germany, The Netherlands, Sweden and Switzerland. A detailed questionnaire was completed and allergen-specific IgE was measured in blood. RESULTS: Growing up on a farm was found to have a protective effect against all outcomes studied, both self-reported, such as rhinoconjunctivitis, wheezing, atopic eczema and asthma and sensitization (allergen specific IgE > or = 0.35 kU/l). The adjusted odds ratio (OR) for current rhinoconjunctivitis symptoms was 0.50 (95% confidence interval (CI) 0.38-0.65) and for atopic sensitization 0.53 (95% CI 0.42-0.67) for the farm children compared to their references. The prevalence of allergic symptoms and sensitization was also lower among Steiner school children compared to reference children, but the difference was less pronounced and not as consistent between countries, adjusted OR for current rhinoconjunctivitis symptoms was 0.69 (95% CI 0.56-0.86) and for atopic sensitization 0.73 (95% CI 0.58-0.92). CONCLUSIONS: This study indicates that growing up on a farm, and to a lesser extent leading an anthroposophic life style may confer protection from both sensitization and allergic diseases in childhood.

Bacterial and fungal agents in house dust and wheeze in children: the PARSIFAL study.

BACKGROUND: Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. This might be related to increased inhalatory exposure to microbial agents. OBJECTIVE: To assess the association between microbial agents in house dust and atopic wheeze in farm children, Steiner school children and reference children. METHODS: Levels of bacterial endotoxin, fungal beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in mattress and living room floor dust were measured in a population of 270 atopic (=Phadiatop-positive) children with self-reported wheezing, including 168 current atopic wheezers, and 441 non-atopic, non-symptomatic controls. These children were selected from a cross-sectional study in five European countries. RESULTS: In the study population as a whole, average levels of mattress dust endotoxin, EPS and glucans were slightly (1.1-1.2-fold; P<0.10) higher in control children than in atopic wheezers. Atopic wheeze was related to mattress levels of endotoxin, EPS and glucans in farm and farm-reference children. However, when adjusting for group (farm vs. farm-reference children), the associations became non-significant whereas the group effect remained. No associations between atopic wheeze and microbial agents were observed in Steiner and Steiner-reference children. For current atopic wheeze, the farm effect became non-significant after adjustment for microbial agent levels. CONCLUSION: Not only bacterial endotoxin but also mould components might offer some protection against atopic wheeze in children. However, the protective effect of being raised on a farm was largely unexplained by the mattress microbial agent levels measured in this study.

Validation of questions on asthma and wheeze in farming and anthroposophic children.

BACKGROUND: In most epidemiological surveys the estimated prevalence of asthma is based on questionnaire responses, which may depend on the individual's perception as well as medical consulting habits in a given population. Therefore, measurement of bronchial hyper-responsiveness as a key feature of asthma has been suggested as an objective parameter for asthma. OBJECTIVE: The aim of the present study was to validate questionnaire responses on asthma and wheeze against bronchial response to hypertonic saline (HS) (4.5%) in populations previously shown to have a lower prevalence of asthma and allergies: farmers' children and children from anthroposophic families. METHODS: Children whose parents had completed a written questionnaire in the cross-sectional PARSIFAL-study were drawn from the following four subgroups: 'farm children' (n=183), 'farm reference children' (n=173), 'Steiner schoolchildren' (n=243) and 'Steiner reference children' (n=179). Overall, 319 children with wheeze in the last 12 months and 459 children without wheeze in the last 12 months performed an HS challenge. RESULTS: Odds ratios, sensitivity, specificity, likelihood ratios and measures of association did not differ significantly between the four subgroups. The correlation between the bronchial response to HS and wheeze and asthma questions was moderate and similar for farm children, farm reference children, Steiner schoolchildren and Steiner reference children (kappa for 'wheeze': 0.25, 0.33, 0.31, 0.35, respectively, P=0.754, kappa for 'doctor's diagnosis of asthma': 0.33, 0.19, 0.33, 032, respectively, P=0.499). CONCLUSION: The findings from this study suggest that the reliabilitiy of questionnaire responses on asthma and wheeze is comparable between farmers' children, children raised in families with anthroposophic lifestyle and their respective peers.

Reduced human growth hormone (hGH) bioactivity without a defect of the GH-1 gene in three patients with rhGH responsive growth failure.

BACKGROUND: A GH deficiency-like phenotype with normal or high hGH secretion, pathologically low IGF-I serum levels, and catch-up growth under treatment with recombinant hGH is suggestive of the presence of biologically inactive hGH syndrome, whose presumably heterogenous molecular basis is substantially unknown. DESIGN: Serum samples from patients who fulfilled the above criteria and from controls with idiopathic short stature were measured by polyclonal hGH-RIA, Nb2 rat lymphoma proliferation assay, and hGH immunofunctional assay (IFA). If assays were suggestive of the presence of bioinactive GH, mutational analysis of the hGH-1 gene was performed. PATIENTS: Three patients were selected because of clinical and biochemical evidence. At the time of diagnosis mean age was 3.4 (2.2, 3.5, 4.5) years, mean height -3.5 (-2.8, -3.6, -4.2) SD score (SDS) and mean growth rate -1.5 (-1.4, -1.5, -1.6) SDS. Mean IGF-I serum levels were -1.9 (-0.7, -2.4, -2.5) SDS and mean IGFBP-3 serum levels -1.2 (-1.1, -1.2, -1.2) SDS. Stimulated and spontaneous GH peaks measured by a polyclonal radioimmunoassay were all above 14 microg/l. GHBP serum levels were normal, and antihGH antibodies were not detected. Therapy with rhGH was effective in causing catch-up growth of the three children with an initial mean growth rate of + 2.9 (+ 1.7, + 2.1, + 5.0) SDS, and normalization of IGF-I (mean: -0.66 SDS: -1.8, - 1.2, + 1.1 SDS) and IGFBP-3 serum levels (mean: + 0.81 SDS: -0.2, + 0.8, + 1.8 SDS). RESULTS: In comparison to controls, the patients' serum hGH levels were much lower when measured by Nb2 rat lymphoma cell proliferation bioassay (mean: -2.3 SDS, range: -1.7- -4.1) and by the immunofunctional assay (IFA) (-1.5 SDS, range: -0.2- -3.1) than by RIA. Retesting of two of the three patients including an one year break of therapy confirmed the rhGH dependence of growth in spite of normal endogenous GH secretion. Radioactive direct sequencing of both strands of PCR-amplified genomic DNA and cDNA excluded a GH-1 gene mutation in all three children. CONCLUSION: Mutations of the GH-1 gene are probably not the main genetic defect in children with biologically inactive hGH syndrome. Posttranslational processing of hGH might reduce the biological activity of the normal translation product.