Polyclonal, newly derived T cells with low expression of inhibitory molecule PD-1 in tonsils define the phenotype of lymphocytes in children with Periodic Fever, Aphtous Stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome.

PURPOSE: PFAPA syndrome is a benign, recurrent inflammatory disease of childhood. Tonsillectomy is one of the therapeutic options with a yet unexplained biological mechanism. We tested whether specific lymphocyte subsets recruited from blood to human tonsils participate in PFAPA pathogenesis. METHODS: Paired tonsils/peripheral blood (PB) samples were investigated (a) from children with PFAPA that successfully resolved after tonsillectomy (n=10) (b) from children with obstructive sleep apnoea syndrome as controls (n=10). The lymphocyte profiles were analysed using 8-colour flow cytometry, immunoglobulin (IGH) and T-cell receptor (TCR) gene rearrangements via PCR and next generation sequencing; a TREC/KREC analysis was performed using qPCR. RESULTS: The PFAPA tonsils in the asymptomatic phase had a lower percentage of B-lymphocytes than controls; T-lymphocyte counts were significantly higher in PB. The percentages of cytotoxic CD8pos T-lymphocytes were approximately 2-fold higher in PFAPA tonsils; the transitional B cells and naïve stages of both the CD4pos and CD8pos T-lymphocytes with a low expression of PD-1 molecule and high numbers of TREC were also increased. With the exception of elevated plasmablasts, no other differences were significant in PB. The expression levels of CXCL10, CXCL9 and CCL19 genes were significantly higher in PFAPA tonsils. The IGH/TCR pattern showed no clonal/oligoclonal expansion. DNA from the Epstein-Barr virus, Human Herpervirus-6 or adenovirus was detected in 7 of 10 PFAPA tonsils but also in 7 of 9 controls. CONCLUSIONS: Our findings suggest that the uninhibited, polyclonal response of newly derived lymphocytes participate in the pathogenesis of PFAPA. Because most of the observed changes were restricted to tonsils and were not present in PB, they partly explain the therapeutic success of tonsillectomy in PFAPA syndrome.

Changes of orexin A plasma levels in girls with anorexia nervosa during eight weeks of realimentation.

OBJECTIVE: Orexin A (OXA) is a hypothalamic neuropeptide involved in regulation of food intake and nutritional status. There are multiple disturbances of neuropeptide signaling described in girls with anorexia nervosa (AN), but OXA levels have not been addressed in this population to date. Therefore, we analyzed OXA levels of AN girls in this study. METHOD: OXA (radioimmunoassay/RIA/method), leptin, insulinlike growth factor-1 (IGF-1), and insulinlike growth factor-1 binding protein-3 (IGFBP-3) levels were measured before and after 8 weeks of realimentation in 36 girls with AN and in 14 healthy controls (control group: CG). RESULTS: Average weight increased significantly in AN during the study (p < .0001), while plasma levels of OXA decreased (before realimentation: 56.2 ± 2.4 pg/ml; after realimentation: 47.5 ± 1.4 pg/ml; p = .0025). OXA levels before realimentation differed from levels in the CG (47.15 ± 2.6 pg/ml, p = .034), but not afterward. We did not find any correlation between OXA and age, height, weight, BMI; or IGF-1, IGFBP-3, and leptin levels. DISCUSSION: OXA levels in untreated AN patients differ significantly from healthy subjects and decrease during realimentation. These findings indicate that OXA may be involved in the nutritional regulation of malnourished children and adolescents.

Spectrum and frequency of SLC26A4 mutations among Czech patients with early hearing loss with and without Enlarged Vestibular Aqueduct (EVA).

Mutations in SLC26A4 cause Pendred syndrome (PS) - hearing loss with goitre - or DFNB4 - non-syndromic hearing loss (NSHL) with inner ear abnormalities such as Enlarged Vestibular Aqueduct (EVA) or Mondini Dysplasia (MD). We tested 303 unrelated Czech patients with early hearing loss (298 with NSHL and 5 with PS), all GJB2-negative, for SLC26A4 mutations and evaluated their clinical and radiological phenotype. Among 115 available HRCT/MRI scans we detected three MD (2.6%), three Mondini-like affections (2.6%), 16 EVA (13 bilateral - 19.2% and 15.6% respectively) and 61 EVA/MD-negative scans (73.4%). We found mutation(s) in 26 patients (8.6%) and biallelic mutations in eight patients (2.7%) out of 303 tested. In 18 of 26 (69%) patients, no second mutation could be detected even using MLPA. The spectrum of SLC26A4 mutations in Czech patients is broad without any prevalent mutation. We detected 21 different mutations (four novel). The most frequent mutations were p.Val138Phe and p.Leu445Trp (18% and 8.9% of pathogenic alleles respectively). Among 13 patients with bilateral EVA, six patients (50%) carry biallelic mutations. In EVA -negative patients no biallelic mutations were found but 4.9% had monoallelic mutations. SLC26A4 mutations are present mostly in patients with EVA/MD and/or progressive HL and those with affected siblings.

Bacterial infection complications in children with cochlear implants in the Czech Republic.

OBJECTIVE: Studies describing wound infections after cochlear implantation are rare. Meticulous operative techniques and sufficient surgical skill can help to avoid severe postoperative complications. Minor complications such as seromas, superficial wound infections, skin emphysema, and swelling can all be successfully treated using conservative methods. Serious problems, however, could be caused by Pseudomonas aeruginosa and Staphylococcus aureus infections. STUDY DESIGN: Retrospective case series. SETTING: Pediatric cochlear implant center in the Czech Republic. RESULTS: In our cohort of 360 children operated on between 1994 and 2009, there were no major surgical complications. However, there were four serious wound infections, two of which resulted in explantation of the device. Two patients with a well-bordered abscess formation were successfully treated with antibiotics and drainage. Explantation was required in another two children with refractory P. aeruginosa infection. Despite favorable sensitivity to a number of antibiotics, intravenous and intensive local treatment failed. After explantation, the operative sites healed immediately. Both children were successfully implanted contralaterally 6 months later. Detailed bacteriological tests from different parts of the device were performed. CONCLUSION: The consequences of explantation were discussed in our cochlear implant center. Confirmed by the microbiological results and reports in the scientific literature, it seems preferable to cut the electrode near the cochlear array and leave it inside the cochlea in order to use the same ear for reimplantation at a later date.

Corrosive injury of the oesophagus in children.

OBJECTIVE: This study examined a cohort of pediatric patients treated for suspected corrosive injury of the oesophagus in the ENT department between 1994 and 2003. METHODS: During the study period we examined 337 patients. All patients were treated according to an individual diagnostico-therapeutic protocol that included: foremost, early rigid oesophagoscopy; intensive medical therapy; nasogastric tube placement; and/or surgical intervention. RESULTS: Our proposed system of grading on a scale from 0 to 4 was used to classify the findings upon oesophagoscopy. One hundred eighty eight patients (55.7%) had a negative exam; 1st degree corrosive injury was present in 58 patients (17.4%); 2nd and 3rd degree injury in 81 patients (24%); and 4th degree was found in 10 patients (3%). CONCLUSIONS: Because the endoscopic findings were positive in 44% of patients with suspected corrosive injury, early rigid oesophagoscopy is indicated in all patients suspected of having corrosive injury even in the absence of clinical symptoms.

Changes in otoacoustic emissions and high-frequency hearing thresholds in children and adolescents.

With the aim of characterizing the loss of high frequency hearing sensitivity in children, hearing thresholds and otoacoustic emissions were measured in a group of 126 normal hearing children and adolescents aged from 6 to 25 years. The subjects were divided into four 5-year age groups. Hearing thresholds over a range of 125 Hz-12.5 kHz were similar in all age groups, the average hearing threshold at 16 kHz was significantly elevated in the oldest age group. The response values of transiently evoked otoacoustic emissions (TEOAEs) significantly declined with age; the decline was negatively correlated with the hearing loss at 16 kHz. Significantly larger TEOAE responses and average distortion-product otoacoustic emission (DPOAE) values at 6.3 kHz were present in the youngest group in comparison with the other three older groups. Spontaneous otoacoustic emissions (SOAEs) were present in 70.8% of the children (in either one or both ears) with the greatest prevalence in the 11-20-year-old subjects. In the 21-25-year-old group, the hearing loss at 16 kHz was significantly smaller in ears with SOAEs than in ears without SOAEs. The results demonstrate that the increase in the high frequency hearing threshold at 16 kHz, which starts at ages over 20 years, is correlated with a decrease in the TEOAE responses at middle frequencies.

Corrosive oesophagitis in children following ingestion of sodium hydroxide granules--a case report.

Over the past few years, the ENT clinic in Motol has noticed an alarming increase in the number of cases of severe upper GIT injury in children, in the majority of cases caused by accidental ingestion of corrosives. Suicidal and homicidal cases in the paediatric population are rare. The following case study describes an interesting episode involving ingestion of granules of the lye NaOH in 13 children of school age. We furthermore stress the importance of early endoscopic investigation in every patient with possible corrosive injury of the oesophagus. We include a brief description of the diagnostico-therapeutic algorithm applied to each such patient that was developed through interdepartmental research in Motol Faculty Hospital.

Aortoesophageal fistula--an unusual complication of esophagitis caused by Dieffenbachia ingestion.

Aortoesophageal fistula (AEF) is a rare and mostly lethal cause of upper gastrointestinal bleeding in children. We report a successful outcome of surgical treatment after resuscitation of a girl aged 12 1/2 years with AEF as a complication of esophagitis caused by Dieffenbachia ingestion. The girl ate a leaf of Dieffenbachia picta in a suicidal attempt. After 5 weeks of medical treatment of esophagitis, small blood-stained vomitus and melena appeared. Within a few hours, it was followed by a massive gastrointestinal bleeding leading to exsanguination. The girl survived despite the pitfalls in clinical presentation and errors in diagnostic approach and treatment. Emergency exploration of cervical esophagus, followed by laparotomy and thoracotomy, was performed in attempt to find the source of bleeding and to control it. Aortoesophageal fistula was located between the ascending aorta near the origin of the brachiocephalic trunk and thoracic esophagus. Resection of the fistula led to prompt circulatory stabilization. The common houseplant, Dieffenbachia picta, causes edematous swelling of mucus membranes when chewed. Dieffenbachia-caused esophagitis is very rare and this etiology of AEF has not been reported in children.

Corrosive oesophagitis in children following ingestion of sodium hydroxide granules--a case report.

Over the past few years, the ENT clinic in Motol has noticed an alarming increase in the number of cases of severe upper GIT injury in children, in the majority of cases caused by accidental ingestion of corrosives. Suicidal and homicidal cases in the paediatric population are rare. The following case study describes an interesting episode involving ingestion of granules of the lye NaOH in 13 children of school age. We furthermore stress the importance of early endoscopic investigation in every patient with possible corrosive injury of the oesophagus. We include a brief description of the diagnostico-therapeutic algorithm applied to each such patient that was developed through interdepartmental research in Motol Faculty Hospital.