Ivo Šlapák

MicroRNAs in chronic lymphocytic leukemia pathogenesis and disease subtypes

MicroRNAs (miRNAs) are short, non-coding RNAs, which function as evolutionary conserved regulators of a gene expression. They have essential roles in development, cell differentiation, proliferation, apoptosis and chromosome structure. MiRNAs constitute about 3–5% of predicted genes in the human genome (i.e. about 1000); and 20–30% of the protein-coding genes are estimated to be regulated by the miRNAs. The primary evidence that miRNAs possibly act as a novel class of oncogenes/tumor-suppressors comes from the discovery of the miR-15a and miR-16-1 in 13q14 region deleted in chronic lymphocytic leukemia (CLL). Moreover, miRNA signatures have been used to classify tumor types. There have recently been several reports on the miRNAs role in CLL pathogenesis and disease subtypes (according to IgVH mutation status). In this report, we will review the published observations and present our miRNA profiling data in aggressive CLL with TP53 abnormalities (deletion and/or mutation of p53 gene). We have identified a deregulated miRNA expression pattern (down regulation of miR-34a, miR-29 and miR-17-5p) in these samples, compared to cells with wild-type TP53. It has previously been shown that miR-34a is directly regulated by p53 and targets BCL-2, miR-29c regulates the MCL-1 and TCL-1 proto-oncogenes and the miR-17-5p targets important cell cycle regulatory molecules. Consequently, these three miRNAs could potentially play important roles in the pathogenesis of aggressive CLL.

Efficacy of Isotonic Nasal Wash (Seawater) in the Treatment and Prevention of Rhinitis in Children

OBJECTIVE To evaluate the potential of nasal isotonic saline application to prevent reappearance of cold and flu in children during the winter. DESIGN Prospective, multicenter, parallel-group, open, and randomized comparison. SETTING Eight pediatric outpatient clinics. PATIENTS A total of 401 children (aged 6-10 years) with uncomplicated cold or flu. INTERVENTIONS We randomly assigned patients to 2 treatment groups, one with just standard medication, the other with nasal wash with a modified seawater solution (Physiomer) plus standard medication, and observed them for 12 weeks. MAIN OUTCOME MEASURES The primary efficacy end points were nasal symptoms resolution during acute illness (visits 1 and 2). We also looked for reappearance of cold or flu, consumption of medication, complications, days off school, and reported days of illness during the following weeks when preventive potential was evaluated (visits 3 and 4). RESULTS At visit 2, patients in the saline group achieved primary end points (measured on a 4-point numeric scale on which 1 indicated no symptoms and 4, severe symptoms) in the parameters nasal secretion and obstruction (mean scores vs nonsaline group, 1.79 vs 2.10 and 1.25 vs 1.58, respectively) (P < .05 for both). During the prevention phase (at visit 3, 8 weeks after study entry) patients in the saline group showed significantly lower scores in sore throat, cough, nasal obstruction, and secretion (P < .05 for all). By visit 3, significantly fewer children in the saline group were using antipyretics (9% vs 33%), nasal decongestants (5% vs 47%), mucolytics (10% vs 37%), and systemic antiinfectives (6% vs 21%) (P < .05 for all). During the same period children in the saline group also reported significantly fewer illness days (31% vs 75%), school absences (17% vs 35%), and complications (8% vs 32%) (P < .05 for all). Similar results were found at the final visit. CONCLUSION Children in the saline group showed faster resolution of some nasal symptoms during acute illness and less frequent reappearance of rhinitis subsequently.

Toys in the upper aerodigestive tract: New evidence on their risk as emerging from the Susy Safe Study

Foreign body (FB) inhalation, aspiration or ingestion are relatively common events in children. Despite many efforts made in several countries to achieve acceptable safety levels for consumer products devoted to children, small toys or toy parts are still frequently mentioned among risky foreign bodies. The aim of the present study is to characterize the risk of complications and prolonged hospitalization due to toys inhalation, aspiration or ingestion according to age and gender of patients, FB characteristics, circumstances of the accident, as emerging from the Susy Safe Registry. The Susy Safe Registry started in the 2005 to collect data to serve as a basis for a knowledge-based consumer protection activity. It is actually one of the wider databases collecting foreign body injuries in the upper aero-digestive tract in pediatric patients. It is distinguished by a deep characterization of objects which caused the injuries and a multi-step quality control procedure which assures its reliability. Preventive strategies imposing a regulation of industrial production, even if fundamental, are not sufficient and need to be integrated along with other intervention addressed to make aware caregivers toward a proper surveillance of children.

Exostosis of the optic canal in a child – a rare diagnosis in a paediatric ear, nose and throat setting: a case report

IntroductionOptic nerve compression is an uncommon disorder leading to deterioration or complete loss of vision.Case presentationWe describe the case of a 14-year-old Caucasian girl with a gradual deterioration of vision in her right eye. Using modern imaging techniques and endonasal endoscopic surgery, we identified the cause and removed the pathology.ConclusionsThe cause of optic nerve compression was a rare exostosis in the optic canal. An endonasal endoscopic approach is the optimal choice for management of optic nerve pathologies. It is a gentle and minimally invasive surgical technique. Interdisciplinary cooperation, especially with the eye doctor and radiologist, is required in these cases.

Post-myringotomy oto-liquorrhea in children - a case study and literature review

Myringotomy is a surgical incision of tympanic membrane used mainly as therapy for acute otitis media. It is a safe and simple procedure; however possible complications must be considered. In this article is described a case study of a 2-and-a-half-year-old girl with a massive oto-liquorrhea following myringotomy.

Histological analysis of retraction pocket pars tensa of tympanic membrane in children

AIMS Histological and histochemical analysis of retraction pocket of pars tensa of tympanic membrane in children. Identification of morphological abnormalities in comparison with a healthy tympanic membrane as it is described in standard textbook. Identification of signs typical for cholesteatoma and support for a retraction theory of cholesteatoma formation. STUDY DESIGN A prospective study analysing 31 samples of retraction pockets taken during surgery. DEPARTMENTS University Hospital, Childrens Medical Centre METHODS Samples of retraction pockets were processed by a standard process for light microscopy, stained by haematoxylin-eosin. Van Giesons stain was used for differential staining of collagen, Verhoeffs stain for elastic fibre tissues, Alcian blue for acidic polysaccharides and PAS (Periodic Acid Schiff) method for basement membrane polysaccharides. RESULTS The following findings were observed in the samples of retraction pockets: hyperkeratosis (100%), hypervascularisations (100%), subepithelial fragmented elastic fibres (96%), myxoid changes (87%), subepithelial inflammatory infiltration (84%), rete pegs (71%), papilomatosis (71%), intraepithelial inflammatory cellularizations, (48%), intraepithelial spongiosis (16%) and parakeratosis (3%). No basement membrane continuity interruptions were observed. Thickness of retraction pocket, thickness of epidermis, occurrence of rete pegs and frequency of fragmented elastic fibres was higher in a Grade III stage RP than Grade II stage RP (according to Charachon). CONCLUSION Morphological abnormalities in the structure of retraction pockets in comparison with a healthy tympanic membrane were described. The changes are typical for a structure of cholesteatoma (these changes are common in matrix and perimatrix), supporting retraction theory of its origin. Our observations show that it is inflammation that probably plays a key role in the pathogenesis of retraction pocket. The frequency of some of the changes increases with the stage of retraction pocket (II-III according to Charachon). Basement membrane continuity interruptions are not typical for retraction pockets.

Risk posed to children by stationery items in the upper airways: evidence emerging from the ESFBI study

Rationale and aim The insertion, inhalation, aspiration or ingestion of a foreign body (FB) is a relatively frequent event in young children. Some classes of objects such as stationery items (including pencils, pens and their parts etc), are frequently listed in clinical registries among commonly inserted, inhaled, aspirated or ingested objects but rarely receive a specific attention. The aim of the present study is to characterise the risk of complications and prolonged hospitalisation due to stationery items according to age and gender of patients, FB characteristics and FB location, circumstances of the accident, as emerging from the ESFBI study. Methods A retrospective study in major hospitals of 19 European countries was realised on children aged 0–14 having inhaled/aspired or ingested a stationery item, with regard to the characteristics of the child and the FB (shape volume consistency), the FB location the hospitalisations details and the occurrence of complications. Results In the years 2000–2003 a total of 2094 FB injuries occurred in children aged 0–14 years. Among them 62 (3%) were due to a stationery item: 32 were due to objects insertion in the ears while 30 occurred in the upper and lower respiratory tract. Objects most frequently involved are parts of pens in children younger than 3 years and eraser in older. 39% of children needed hospitalisation. The most documented complication was inflammation of external ear. Almost 24% of injuries happened under adults supervision. Conclusions Injuries are events that in many cases can be prevented with appropriate strategies. Passive environmental strategies, including product modification by manufacturers, are the most effective. However, regulation regarding small parts of potentially dangerous objects, covers products addressed to children use but objects not projected for children, such as stationary items, are excluded. Our study testifies that stationary is involved in a non-negligible percentage of FB injuries, mainly due to insertion in the ears. Frequently, injuries happens under adult supervision. This results confirm the fact that when passive preventive strategies are not practical, active strategies that promote behaviour change are necessary and information about this issue should be included in all visits to family paediatricians.