[Orbital Fractures in Children]. / Fraktura orbity v detském veku.

PURPOSE OF THE STUDY Diagnosis and treatment of fractures of the facial skeleton in children can be difficult due to the skeletal growth. MATERIAL AND METHODS The 9-year retrospective study included patients admitted with the orbital fracture diagnosis to the University Hospital Brno, Children s Hospital, Department of Paediatric ENT, Department of Paediatric Anaesthesiology and Resuscitation, and Department of Paediatric Surgery, Orthopaedics and Traumatology. We looked into the number of patients admitted to the hospital with the orbital fracture diagnosis and the cause of the injury, the age of patients, and the used treatment method - surgical or non-operative treatment were analysed. The following assumptions were applied: 1. Incidence of the injury (orbital fracture) increases with the age of the patient, 2. Incidence of the injury in individual years is constant. RESULTS In the followed-up period, between 2010 and 2018, a total of 47 patients, of whom 8 girls and 39 boys, with the orbital fracture diagnosis were treated. 12 patients underwent surgery, 35 patients were treated non-operatively. The study group included 47 patients with the age range of 1 to 18 years, with the median age 12 years. When the results were processed, a trend was revealed showing an increase in the number of injuries as well as an in the age of patients at the time of injury. The number of injuries increases with age and year. Both the correlations, however, are statistically insignificant and the trend can be considered statistically insignificant. DISCUSSION Both the non-operative and surgical treatment of patients lead to excellent results, even in the long-term follow-up. In paediatric patients, the surgical approach should be opted for only in cases when the non-operative approach is impossible due to the extent and characteristics of fracture and damage to soft tissues. CONCLUSIONS The surgical treatment aims at the best possible anatomical reconstruction of the orbit with no subsequent functional or cosmetic defects. If surgical treatment is necessary, then the transconjunctival approach is most appropriate in children, namely because of the good overview over the operating field, simple procedure as well as the cosmetic outcome. In most cases it is enough to reposition the orbital soft tissues. In complicated cases, with an orbital floor defect, it needs to be covered with a suitable material. Also, the non-operative approach has its place in therapy and the case-by-case approach must be applied. Orbital fractures should always be treated by experienced specialists (ENT, dental surgeon, traumatologist) specialising in paediatric patients. Key words: fracture, orbit, childhood, surgical, non-operative treatment.

Evolutionary concept of inflammatory response and stroke.

The immune system plays an important role under both physiological and pathological conditions. Immune surveillance as well as defense and healing processes are crucial for the organism, but the immune system has a natural tendency to act aggressively when excessively stimulated. We may assume that the immune system is not designed to deal with severe conditions, such as polytrauma or severe stroke, because these are not compatible with life in the wilderness and evolution has no chance to act in such cases. These conditions are associated with exaggerated/deregulated inflammatory response, which may cause more damage than initial pathology. In this article, we would like to sketch a basic concept of the immune system-brain interactions from the evolutionary point of view and to discuss some implications related to stroke.

The Role of Inflammatory Response in Stroke Associated Programmed Cell Death.

Stroke represents devastating pathology which is associated with a high morbidity and mortality. Initial damage caused directly by the onset of stroke, primary injury, may be eclipsed by secondary injury which may have a much more devastating effect on the brain. Primary injury is predominantly associated with necrotic cell death due to fatal insufficiency of oxygen and glucose. Secondary injury may on the contrary, lead apoptotic cell death due to structural damage which is not compatible with cellular functions or which may even represent the danger of malign transformation. The immune system is responsible for surveillance, defense and healing processes and the immune system plays a major role in triggering programmed cell death. Severe pathologies, such as stroke, are often associated with deregulation of the immune system, resulting in aggravation of secondary brain injury. The goal of this article is to overview the current knowledge about the role of immune system in the pathophysiology of stroke with respect to programmed neuronal cell death as well as to discuss current therapeutic strategies targeting inflammation after stroke.

Genetic risk factors of cisplatin induced ototoxicity in adult patients.

Ototoxicity is an important adverse effect of using Cisplatin (cis-diamminedichloroplatinum) (CDDP) as a form of chemotherapy. The clinical picture of CDDP induced ototoxicity includes perceptive hearing impairment (reversible or permanent) and tinnitus. Ototoxicity manifests with considerable variability between patients. The objective of this prospective study was to investigate a possible genetic background to this variability. We assessed ototoxicity induced by therapeutic doses of CDDP in adult patients with germinative testicular tumors, or other tumors treated with an identical CDDP dosage scheme. Audiological examination before, during and after the treatment has shown deterioration in hearing; first in the high-frequencies and with increased CDDP cumulative doses, impairment in other frequencies as well. Occurrence of tinnitus was not dependent on the administered dose of CDDP, or the other risk factors examined in this study. The association of CDDP induced ototoxicity with genetic polymorphisms in candidate genes was examined. Our study has demonstrated an association of early onset of CDDP induced ototoxicity with the presence of two copies of GSTT1 gene (p=0,009) and with T allele of rs9332377 polymorphism in COMT gene (p=0,001).

Association between three single nucleotide polymorphisms in eotaxin (CCL 11) gene, hexanucleotide repetition upstream, severity and course of coronary atherosclerosis.

The impact of three single-nucleotide polymorphisms in eotaxin (SCYA11) gene promoter (-426C>T and -384A>G) and first exon (67G>A) and recently described hexanucleotide (GAAGGA)(n) 10.9 kb upstream on coronary atherosclerosis was investigated. Elective coronary angiography of 1050 consecutive subjects was performed. All patients were genotyped for the three SNPs. In a subset of the first 472 samples, the number of (GAAGGA)(n) repetitions was determined. For further evaluation, short and long variants were distinguished; the borderline corresponded with the median value of all alleles: ≤8 repetitions were considered as short sequence, ≥9 repetitions as long. Patients with bronchial asthma or insignificant atherosclerosis were excluded; the remaining group of 933 subjects was further investigated. Patients were grouped according to the form of CAD (ACS vs. stable angina) and the number of diseased vessels. The GG variant of 67 G>A polymorphism was associated with acute form of CAD compared to stable angina (p=0.0011, p(corr.)=0.013). The number of (GAAGGA)(n) repetitions in our set of patients ranged from 3 to 12. There were no subjects with 4 or 5 repetitions. The frequency of short repetition alleles increased with the number of affected vessels (1 vs. 3 diseased vessels: p=0.0043, p(corr)=0.034). In our study, the (GAAGGA)(n) hexanucleotide was associated with the severity of CAD. The 67 GG was associated with acute form of CAD. None of the two SNPs in eotaxin promoter had any relation to CAD. The number of (GAAGGA)(n) repetitions can thus be a novel genetic marker of the extent of CAD.

[Genetic background of cisplatin induced ototoxicity]. / Genetické pozadí ototoxicity cisplatiny.

BACKGROUND: Cisplatin induced ototoxicity is a serious adverse effect of cisplatin therapy. Cisplatin induced ototoxicity shows significant interindividual variability. This variability is probably based on genetic background. Recent papers describe association of cisplatin ototoxicity with allelic variants of glutathion-S-transferase coding genes. PATIENTS AND METHODS: We have analyzed 55 patients treated with cisplatin therapy without any previous hearing impairment. Audiometric examination was performed before the start of cisplatin therapy and then before and after each cycle of cisplatin. DNA isolated from peripheral blood samples was used to analyze genetic polymorphisms of selected genes coding for glutathion-S-transferases. RESULTS: We have demonstrated association of early onset of cisplatin induced hearing impairment with absence of null allele of GSTT1 (p = 0.009). Both GSTM1 gene deletion and single nucleotide polymorphism in GSTP1 gene (rs1695) did not show any association with cisplatin induced ototoxicity. CONCLUSION: Early onset of cisplatin induced hearing impairment is more probable in persons with two functional alleles of GSTT1 gene.

Expression of p53, cyclin D1 and EGFR correlates with histological grade of adult soft tissue sarcomas: a study on tissue microarrays.

Soft tissue sarcomas (STSs) are rare heterogeneous tumors with variable clinical course and outcome. The management of STSs depends upon the accurate histopathological diagnosis and assessing their histological grade. Currently, core needle biopsies are becoming increasingly popular for diagnosing STSs but value of histological grading is limited from this type of specimens. To evaluate the immunohistochemical expression of p53, mdm-2, cyclin D1, p16, nm23, EGFR and Ki-67 labelling index in adult STSs patients and their association with histological grade of STSs, we analysed 101 primary untreated STSs of the limbs and trunk using the tissue microarray technique on formalin-fixed, paraffin-embedded tissue samples. The cases consisted of 15 G1, 28 G2 and 58 G2 sarcomas. Ki-67 labelling index (LI) was calculated from whole block sections for the possibility to select the most proliferative regions. The LI ranged from 1.26 to 75.5% (median 26.7%) and strongly correlated with the mitotic count (p rs for adult patients with STSs and may assist in establishment of the histological grade in STSs.

Genetic variations in the matrix metalloproteinase-1 promoter and risk of susceptibility and/or severity of chronic periodontitis in the Czech population.

OBJECTIVES: Matrix metalloproteinase-1 (MMP-1) is a potent enzyme degrading extracellular matrix that was implicated in the pathogenesis of chronic periodontitis. Therefore, the aim of our study was to examine the association between three promoter polymorphisms of the MMP-1 gene and chronic periodontitis susceptibility and/or severity in a Czech population. MATERIALS AND METHODS: A total of 329 Caucasian subjects were enrolled in this study. They were 133 patients with mild to severe chronic periodontitis and 196 unrelated control subjects. MMP-1 promoter polymorphisms (-1607 1G/2G, -519A/G, and -422A/T) were genotyped using standard polymerase chain reaction-restriction fragment length product methods. RESULTS: Genotype analysis of the three single nucleotide polymorphisms across 27 different combinations showed significant association with chronic periodontitis (p<0.05). Analyses of individual polymorphisms showed no differences in distribution of the -519A/G and -422A/T variants between periodontitis and control groups. However, a trend to increased frequency of the -1607 1G allele was observed in patients with chronic periodontitis compared with the controls (p=0.054). When the groups were further stratified by smoking status, the 1G allele was associated with chronic periodontitis among non-smokers but not among smokers (p=0.033). On the contrary, the distribution of genotype frequencies of the MMP-1 -422A/T polymorphism was different between the patient and control smokers with respect to heterozygotes (73.91% versus 50.91%; p=0.017). CONCLUSIONS: Our results demonstrate that the polymorphisms in the MMP-1 promoter may have only a small effect on the etiopathogenesis of chronic periodontitis.

Polymorphism Ncol in tumor necrosis factor B is associated with fasting glycemia and lipid parameters in healthy non-obese caucasian subjects.

BACKGROUND: The study was designed to investigate the associations among polymorphisms TNF-B Ncol and TNF-alpha -308G/A, plasma TNF-alpha levels and metabolic and anthropometric parameters related to insulin sensitivity in a set of 113 Caucasian subjects undergoing oral glucose tolerance test (oGTT). METHODS: Genotypes were detected by PCR; BMI, WHR, glycemia during oGTT, fasting immunoreactive insulin, fasting C-peptide, HbA(1c), total cholesterol, triglycerides, HDL, LDL and plasma TNF-alpha levels were measured in each subject. RESULTS: Type 2 diabetes was diagnosed in 10 subjects, impaired glucose tolerance (IGT) in 41, normal glucose tolerance (NGT) in 62. Significant differences among genotypes of the TNF-B Ncol were observed for FPG (P=0.0063), LDL (P=0.0179) and marginally for total cholesterol (P=0.0763) in NGT group. After the classification of NGT subjects into obese and non-obese according to BMI, associations of TNF-B Ncol with FPG, LDL and cholesterol were proved in non-obese subgroup only. TNF-alpha -308G/A polymorphism was not associated with any of the parameters studied. TNF-alpha levels did not revealed difference among NGT, IGT and DM groups or genotype-dependent differences. CONCLUSIONS: Our results indicate significant association of the TNF-B Ncol polymorphism with FPG, LDL and total cholesterol in normoglycemic non-obese Caucasian subjects. This polymorphism could be involved in genetic modulation of glucose and lipid homeostasis and regulation of insulin sensitivity already in healthy state. Disturbances of this regulation could be component of pathogenesis of type 2 diabetes mellitus.

A newly identified single nucleotide polymorphism in the promoter of the matrix metalloproteinase-1 gene.

Matrix metalloproteinase-1 (MMP-1) is a member of the matrix metalloproteinase enzyme family that degrades components of the extracellular matrix. Recent studies have demonstrated several polymorphic sites in the promoter of the MMP-1 gene. A newly identified single nucleotide polymorphism (SNP) at position -519 in the promoter region of the MMP-1 gene is reported. This polymorphism consists in a guanine to adenine substitution. A linkage between polymorphisms -519A/G and -1607 1G/2G was also studied.

Lack of an association of a single nucleotide polymorphism in the promoter of the matrix metalloproteinase-1 gene in Czech women with pregnancy-induced hypertension.

In preeclampsia the cytotrophoblast invasion of the decidual vessels is reduced. The endothelia in the decidual vessels may influence cytotrophoblast invasion and remodeling of decidual spiral arteries. The decidual endothelial cells from preeclamptic placentas produce less matrix metalloproteinase-1 (MMP1) than those from normal placentas. MMPs form a group of enzymes that are capable of degrading components of extracellular matrix. The present study investigated the prevalence and possible association of an insertion of guanine in the promoter of the MMP1 gene in pregnancy-induced hypertension, preeclampsia and eclampsia in the Czech population. This was a case-control study. No differences were observed in genotype frequencies between cases and controls. The insertion of the guanine in the promoter of the MMP1 gene does not appear to increase the risk of development of pregnancy-induced hypertension, preeclampsia and eclampsia.