Ünal Uluca

Bacterial agents causing meningitis during 2013–2014 in Turkey: A multi-center hospital-based prospective surveillance study

ABSTRACT This is an observational epidemiological study to describe causes of bacterial meningitis among persons between 1 month and 18 y of age who are hospitalized with suspected bacterial meningitis in 7 Turkish regions. covering 32% of the entire population of Turkey. We present here the results from 2013 and 2014. A clinical case with meningitis was defined according to followings: any sign of meningitis including fever, vomiting, headache, and meningeal irritation in children above one year of age and fever without any documented source, impaired consciousness, prostration and seizures in those < 1 y of age. Single tube multiplex PCR assay was performed for the simultaneous identification of bacterial agents. The specific gene targets were ctrA, bex, and ply for N. meningitidis, Hib, and S. pneumoniae, respectively. PCR positive samples were recorded as laboratory-confirmed acute bacterial meningitis. A total of 665 children were hospitalized for suspected acute meningitis. The annual incidences of acute laboratory-confirmed bacterial meningitis were 0.3 cases / 100,000 population in 2013 and 0.9 cases/100,000 in 2014. Of the 94 diagnosed cases of bacterial meningitis by PCR, 85 (90.4%) were meningococcal and 9 (9.6%) were pneumococcal. Hib was not detected in any of the patients. Among meningococcal meningitis, cases of serogroup Y, A, B and W-135 were 2.4% (n = 2), 3.5% (n = 3), 32.9% (n = 28), and 42.4% (n = 36). No serogroup C was detected among meningococcal cases. Successful vaccination policies for protection from bacterial meningitis are dependent on accurate determination of the etiology of bacterial meningitis. Additionally, the epidemiology of meningococcal disease is dynamic and close monitoring of serogroup distribution is comprehensively needed to assess the benefit of adding meningococcal vaccines to the routine immunization program.

Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

High frequency of E148Q sequence variation in children with familial Mediterranean fever in southeast Turkey

OBJECTIVE The aim of this study was to investigate the spectrum of Mediterranean fever (MEFV) gene mutations and genotype-phenotype correlation in children with familial Mediterranean fever (FMF) in southeast Turkey. METHODS A total of 507 children (274 females) with FMF and MEFV gene mutation(s) were included. A 15-year retrospective evaluation was conducted; parameters analyzed were: age, sex, age at symptoms onset, age at FMF diagnosis, delay between symptoms onset and diagnosis, FMF attack symptoms, and response to colchicine. Disease severity scores were calculated and MEFV mutation analysis was performed via real-time PCR for the 6 most frequent mutations. Children with comorbid diseases or tested negative for MEFV gene mutations were excluded to provide homogeneity. RESULTS A family history of FMF was found in 60.2% (n=305) of patients. The most common symptoms reported for FMF attacks were abdominal pain (98.0%), fever (93.9%) and arthralgia (47.3%); 75.0% of patients (n=380) were heterozygous, 14.2% were homozygous (n=72) and 10.8% were compound heterozygous (n=55).The following MEFV gene mutation alleles were identified: E148Q (40.1%), M694V (25.9%), V726A (15.8%), R761H (7.4%), M680I (6.8%), and P369S (4.1%). The M694V subgroup had the lowest mean age of disease onset and the highest mean disease severity score, whereas the E148Q group had later mean disease onset and the lowest mean disease severity score (p<0.05). CONCLUSION The highest E148Q mutation frequency and milder disease in the course of FMF in our study population may be due to geographic and ethnic background dissimilarities of southeast Turkey.

Usefulness of Mean Platelet Volume and Neutrophil-to-Lymphocyte Ratio for Evaluation of Children with Familial Mediterranean Fever

Background Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of serositis, fever, and rash. Clinical and subclinical inflammatory processes may contribute to atherosclerosis in FMF patients, with mean platelet volume (MPV) as a potential indicator for atherosclerosis risk and neutrophil-to-lymphocyte ratio (NLR) as a marker for subclinical inflammation in these patients. In this study, we investigated whether MPV can be used as an indicator for atherosclerosis risk and if NLR is a marker for subclinical inflammation in FMF patients. Material/Methods The study consisted of 75 FMF patients in attack, 157 attack-free patients, and 77 healthy controls. White blood cell count neutrophil-to-lymphocyte ratio, platelet count, MPV, PDW C-reactive protein levels, and erythrocyte sedimentation rate were recorded. Results There were no significant differences between attack, attack-free, and control groups in terms of mean MPV and PDW value. NLR value was higher in the attack group. NLR value was similar in attack-free and control groups. Conclusions We found that MPV and PDW values are similar in FMF patients and healthy controls. NLR was higher in FMF patients in the attack period. Therefore, our results suggest that MPV and PDW values do not predict atherosclerosis risk in pediatric FMF patients, and NLR may be an indicator for attack period but not attack-free period.

Assessment of epicardial adipose tissue thickness and the mean platelet volume in children with familial Mediterranean fever.

BackgroundFamilial Mediterranean fever (FMF) is an inflammatory disease, which is suggested to be associated with increased risk of atherosclerosis. Epicardial adipose tissue (EAT) thickness and the mean platelet volume (MPV) are parameters used in prediction of atherosclerotic risk in various conditions. These parameters were evaluated in children with FMF and compared with healthy controls.MethodsForty-five patients with FMF and 54 age- and gender-matched healthy controls were assessed. Duration of symptoms, age at diagnosis, duration of delay in diagnosis, frequency and duration of FMF attacks, disease severity scores, response to colchicine therapy, MEditerraneanFeVer (MEFV) gene mutations, and MPV values were recorded. EAT thicknesses were measured by echocardiography.ResultsEpicardial adipose tissue thicknesses of the children with FMF were found to be significantly greater than that of controls (5.1 ± 1.4 vs. 4.5 ± 0.9 mm, p = 0.036). FMF patients had significantly higher MPV values compared with the controls (7.8 ± 1.1 vs. 7.3 ± 1.4 fl, p = 0.044). Age at diagnosis, duration of delay in diagnosis, and MPV values were found to be correlated with EAT thickness in the patient group (r = 0.49, p = 0.001 for the former parameters and r = 0.32, p = 0.04 for MPV).ConclusionEpicardial adipose tissue thickness and MPV values seem to be increased in children with FMF. These findings may indicate an increased risk of atherosclerosis in FMF patients.

The spectrum of MEFV gene mutations and genotypes in Van province, the eastern region of Turkey, and report of a novel mutation (R361T)

Familial Mediterranean fever (FMF) is the most common hereditary inflammatory periodic disease, characterized by recurrent episodes of fever and abdominal pain, synovitis, and pleuritis. The aim of this study was to determine the frequency and distribution of Mediterranean fever (MEFV) gene mutations in Van province of Eastern Anatolia and to compare them with the other studies from various regions of Turkey. Therefore, we retrospectively evaluated MEFV gene mutations in 1058 pediatric patients with suspected FMF. The MEFV gene mutations were investigated using Sanger sequencing and the multiplex minisequencing technique. We identified 37 different genotypes and 16 different mutations. The four most common mutations and allelic frequencies were M694V (36.50%), E148Q (32.77%), V726A (14.09%), and M694I (4.41%). M694V was the most common mutation, and the M694I frequency was found to be higher compared to studies from other regions of Turkey. In addition, we identified a novel missense mutation (R361T, c.1082G>C) in exon 3 of the MEFV gene in a 12-year-old boy, who had a typical FMF phenotype. In conclusion, this study evaluated the distribution of MEFV gene mutations in children with FMF as the first study conducted in Van province, Eastern Anatolia.

Urinary Kidney Injury Molecules in Children with Iron-Deficiency Anemia

Background The aim of this study was to investigate the urine levels of human kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with iron-deficiency anemia (IDA). Material/Methods Thirty-five children with IDA and 32 matched healthy controls were recruited. We assessed complete blood count, serum iron, iron-binding capacity, ferritin, serum levels of urea, creatinine (Cr), sodium (Na), potassium (K), calcium (Ca), and glucose levels. Estimated glomerular filtration rate (eGFR) was calculated. Urinary NAG, NGAL, KIM-1, and L-FABP were measured and divided by urine creatinine for comparisons. Results There were no significant differences in serum urea, Cr, or eGFR between the IDA group and the control group (p>0.05, for all). IDA patients had significantly higher urine NGAL/Cr, L-FABP/Cr, KIM-1/Cr, and NAG/Cr compared with the control group (p<0.05). There were significant negative correlations between hemoglobin, hematocrit, red blood cell count, and urine NGAL/Cr, NAG/Cr, L-FABP/Cr, KIM-1/Cr levels (p<0.05). Conclusions Higher urinary kidney injury molecule levels in IDA patients suggest a possible subclinical renal injury in pediatric IDA patients whose renal functions and serum electrolytes were normal.

Serum galectin-3 levels in children with chronic hepatitis B infection and inactive hepatitis B carriers.

Background Chronic hepatitis B virus (HBV) infection is common worldwide. Follow-up of patients by the use of non-invasive techniques may be valuable in clinical practice. The aim of this study was to investigate serum galectin-3 (GAL-3) levels for monitoring disease status in children with chronic HBV infection. Material/Methods Thirty-two patients with chronic hepatitis B (CHB), 30 inactive HBV carrier patients, and 30 matched healthy controls were enrolled in the study. We performed basic laboratory tests: serum glucose, albumin, alanine aminotransferase (ALT), aspartate aminotransferase, gamma-glutamyl transferase (GGT), total bilirubin, prothrombin time, and activated partial thromboplastin time. In addition, serum GAL-3 levels were measured by ELISA technique. Results Significantly higher serum GAL-3 levels (16.5±3.6, 1.1±0.3, 0.7±0.5 ng/ml, respectively, p<0.001) and ALT levels (80.2±30.6, 26.8±12.6, 28.1±4.4 IU/L, respectively, p<0.001) were found in the CHB group compared with the inactive carriers and the control groups. There were no significant differences in ALT levels and GAL-3 levels or between inactive HBV carriers and the control groups (p>0.05, for each). Significantly higher GGT levels were found in the CHB group (51.3±27.5 IU/L) compared with the inactive HBV carriers (35.7±10.1 IU/L) and the control group (31.3±9.5 IU/L) (p<0.001, and p=0.004, respectively). A significant correlation was found between GAL-3 and ALT levels in the CHB group (r=0.82, p<0.001). Conclusions Our results suggest that serum GAL-3 level may be a beneficial indicator of chronicity in hepatitis B infection in children.

Rapid and Easy Diagnosis of Netherton Syndrome with Dermoscopy

Background: Netherton syndrome is a rare autosomal recessive disease demonstrating ichthyosis linearis circumflexa, atopic findings, and hair shaft anomalies. Trichorrhexis invaginata is the pathognomonic hair shaft anomaly seen in this syndrome. Objective: In recent years, hair shaft anomalies have been described as “matchstick” and “golf tee” signs. We present a patient with Netherton syndrome diagnosed by the presence of matchstick and golf tee hairs in addition to trichorrhexis invaginata.

Urinary early kidney injury molecules in children with beta-thalassemia major.

Abstract Background: The aim of this study was to investigate novel urinary biomarkers including N-acetyl-β-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and liver-type fatty acid binding protein (L-FABP) in children with β-thalassemia major (β-TM). Materials and methods: Totally, 52 patients (29 boys, 23 girls) with β-TM and 29 healthy controls (3–17 years) were included. Various demographic characteristics and blood transfusions/year, disease duration, and chelation therapy were recorded. Serum urea, creatinine, electrolytes, and ferritin and urinary creatinine, protein, calcium, phosphorus, sodium, potassium, and uric acid in first morning urine samples were measured and estimated glomerular filtration rate (eGFR) was calculated. Routine serum and urinary biochemical variables, urinary NAG to Creatinine (UNAG/Cr), UNGAL/Cr, UKIM-1/Cr, and UL-FABP/Cr ratios were determined. Results: Patients had similar mean serum urea, creatinine and eGFR levels compared with controls (p > 0.05 for all). The mean urinary protein to creatinine (UProtein/Cr) ratio was significantly higher in patients compared to the healthy subjects (0.13 ± 0.09 mg/mg and 0.07 ± 0.04 mg/mg, respectively; p < 0.001). Significantly increased UNAG/Cr (0.48 ± 0.58 vs. 0.23 ± 0.16, p = 0.026) and UNGAL/Cr (22.1 ± 18.5 vs. 11.5 ± 6.17, p = 0.01) ratios were found in β-TM patients compared with healthy controls. However, no differences were found in serum and urinary electrolytes or UKIM-1/Cr and UL-FABP/Cr ratios between patients and controls (p > 0.05). Significant correlations were found between urinary biomarkers and urinary electrolytes (p < 0.05). Conclusions: Our results suggest that urinary NAG and NGAL may be considered to be reliable markers to monitor renal injury in β-TM patients.