Managing children with chronic myeloid leukaemia (CML)

Chronic myeloid leukaemia in children and young people is a relatively rare form of leukaemia that shows increased incidence with age and some evidence suggests that the molecular basis differs from that in adults. Significant advances in targeted therapy with the development and use in children of tyrosine kinase inhibitors and the ability to monitor and understand the prognostic significance of minimal residual disease by standardized molecular techniques has shifted the management of this condition from bone marrow transplantation as the main therapeutic modality to individualized treatment for each patient based on achieving specific milestones. The physiological changes occurring during childhood, particularly those affecting growth and development and the long‐term use of treatment, pose specific challenges in this age group, which we are only beginning to understand.     

First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer

Purpose  

Panitumumab monotherapy is approved for KRAS wild-type (WT) metastatic colorectal cancer (mCRC) progressing after standard chemotherapy. This study evaluated first-line panitumumab plus FOLFIRI in patients with mCRC.     

Sport mit Typ-1-Diabetes

Die Diabetologie - Die vielfältigen positiven gesundheitlichen Wirkungen sportlicher Aktivität sind unbestritten. Sport bedeutet für viele Menschen aber deutlich mehr: ein Stück...     

Urinary bladder cancer risk factors in an area of former coal,iron, and steel industries in Germany

ABSTRACT

This study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped. The bladder cancer risk in varnishers and underground hard coal miners was increased as previously shown in a study in this area performed in the 1980s. The occupation of a car mechanic was associated with a significantly elevated bladder cancer risk and higher in the case of underground hard coal miners even though the mine was closed in 1987. The frequency of GSTM1 negative genotype was comparable in cases and controls (53% versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62% versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was 23% versus 15%. An occupational history of a varnisher or an underground hard coal miner remains a risk factor for bladder cancer occurrence. Data indicate that in the case of bladder cancer, GSTM1 is a susceptibility factor related to environmental and/or occupational exposure.     

From chemosensory thresholds to whole body exposures—experimental approaches evaluating chemosensory effects of chemicals

Objectives: To ensure safety and health the avoidance of adverse chemosensory effects is essential at workplaces where volatile chemicals are used. The present study describes psychophysical approaches that provide information for the evaluation of such effects. Methods: By means of a modified staircase procedure the odor (OT) and irritation thresholds (IT) of 15 irritants were determined. These basic chemosensory properties, confining the chemosensory effect range, were investigated in a random sample of 144 persons stratified for gender and age. Those irritants exhibiting high chemosensory potency were selected for the second psychophysical part of the study. Forty-eight persons, again stratified for gender and age, rated the intensity of 13 trigeminal and olfactory perceptions elicited by nine ascending concentrations of the irritants, ranging from the odor to the irritation threshold of the respective substances. Results: Across the investigated chemicals the transition from concentrations eliciting pure olfactory stimulation (OT) to trigeminal stimulation (IT) differed markedly. The carboxylic acids yielded narrow ranges from odor to irritation thresholds, while for the amines (cyclohexylamine, dimethylamine, and trimethylamine) and the esters (ethyl formate and ethyl acetate) these ranges were somewhat wider. The two chemosensory thresholds of ethyl acrylate and ammonia were farthest from each other. Gender and age had only weak impact on the chemosensory thresholds. At present, the results of the intensity ratings could be given for six substances. Among them, the rated pungency for cyclohexylamine, formic acid, and ethyl acetate increased strongest across the nine applied concentrations. Conclusions: By means of these psychophysical approaches a diverse class of chemicals can be described and compared with respect to their chemosensory potency. This information can be used twofold (a) for the evaluation of existing studies reporting sensory irritations and (b) for the design of experimental exposure studies.     

p53 mutations have no additional prognostic value over stage in bladder cancer.

Evidence is accumulating that the tumour-suppressor gene p53 is involved in the development of bladder cancer. Therefore we studied p53 mutations in 47 bladder cancers obtained from 45 patients using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Eight out of 24 invasive tumours appeared to have a p53 mutation, while no p53 mutations were found in the superficial tumours. All the p53 mutations were found in grade 3 tumours. The tumours with altered p53 showed a higher frequency of allelic loss (FAL) than the tumours without a mutation (55.8% vs 21.1%, P < 0.05, chi 2 test). This increase in FAL suggests a correlation between p53 mutations and genetic instability. A significant correlation between mutated p53 and poor survival in the whole group studied was found (P < 0.001, log-rank test). However, within the group of muscle-invasive tumours the occurrence of p53 mutations had no additional prognostic value. Therefore, even though p53 mutations were found in aggressive tumours, the clinical usefulness of its detection seems limited. Nevertheless, these results imply that p53 is involved in the clinical behaviour of bladder cancer; its role in the progression of superficial cancer to invasive disease merits further attention.