Daily Practice of Mechanical Ventilation and Weaning in Turkish PICUs: A Multicenter Prospective Survey.

OBJECTIVES: To investigate conventional mechanical ventilation weaning characteristics of patients requiring conventional mechanical ventilation support for greater than 48 hours within the PICU. DESIGN: The prospective observational multicenter cohort study was conducted at 15 hospitals. Data were being collected from November 2013 to June 2014, with two designated researchers from each center responsible for follow-up and data entry. SETTING: Fifteen tertiary PICUs in Turkey. PATIENTS: Patients between 1 month and 18 years old requiring conventional mechanical ventilation for greater than 48 hours were included. A single-center was not permitted to surpass 20% of the total sample size. Patients with no plans for conventional mechanical ventilation weaning were excluded. INTERVENTIONS: Conventional mechanical ventilation MEASUREMENTS AND MAIN RESULTS:: Pertinent variables included PICU and patient demographics, including clinical data, chronic diseases, comorbid conditions, and reasons for intubation. Conventional mechanical ventilation mode and weaning data were characterized by daily ventilator parameters and blood gases. Patients were monitored until hospital discharge. Of the 410 recruited patients, 320 were included for analyses. A diagnosis of sepsis requiring intubation and high initial peak inspiratory pressures correlated with a longer weaning period (mean, 3.65 vs 1.05-2.17 d; p < 0.001). Conversely, age, admission Pediatric Risk of Mortality III scores, days of conventional mechanical ventilation before weaning, ventilator mode, and chronic disease were not related to weaning duration. CONCLUSIONS: Pediatric patients requiring conventional mechanical ventilation with a diagnosis of sepsis and high initial peak inspiratory pressures may require longer conventional mechanical ventilation weaning prior to extubation. Causative factors and optimal weaning for this cohort needs further consideration.

Therapeutic plasma exchange in primary hemophagocytic lymphohistiocytosis: Reports of two cases and a review of the literature.

We report two children who were diagnosed as having primary hemophagocytic syndrome and who successfully underwent therapeutic plasma exchange (TPE). The first patient was a 6-month-old girl diagnosed with HLH who was admitted to the pediatric intensive care unit. The patient's clinical condition worsened on the 9th day of the HLH-2004 treatment protocol. Her ferritin level was found 50.000 ng/mL, and TPE was performed for 9 sessions, after which her clinical condition and laboratory findings improved. The patient is still on the HLH-2004 protocol and waits for a suitable stem cell transplantation donor. Case 2 involved a Syrian girl with HLH under follow-up who was receiving the HLH-2004 treatment protocol for reactivation. She presented to emergency department with fever, where her ferritin level was measured greater than 100.000 ng/mL; she was then transferred to the pediatric intensive care unit where four sessions of TPE were performed, after which her clinical condition and laboratory findings improved. However, the patient was admitted again one month later with gastrointestinal bleeding and died despite all efforts. By describing these two cases, we wish to emphasize that TPE can produce a rapid improvement until the time of stem cell transplantation in patients with hemophagocytic syndrome who do not respond to traditional treatments.

Critically ill children with pandemic influenza (H1N1) in pediatric intensive care units in Turkey.

OBJECTIVES: To outline the epidemiologic features, clinical presentation, clinical courses, and outcomes in critically ill children with pandemic influenza in pediatric intensive care units. DESIGN: Retrospective, observational, multicenter study. SETTING: Thirteen tertiary pediatric intensive care units in Turkey. PATIENTS: Eighty-three children with confirmed infection attributable to pandemic influenza detected by reverse-transcriptase polymerase chain reaction assay between November 1 and December 31, 2009 who were admitted to critical care units. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During a 2-month period, 532 children were hospitalized with pandemic influenza and 83 (15.6%) needed critical care. For the 83 patients requiring critical care, the median age was 42 (range, 2-204) months, with 24 (28.9%) and 48 (57.8%) of patients younger than 2 and 5 yrs, respectively. Twenty (24.1%) patients had no underlying illness, but 63 (75.9%) children had an underlying chronic illness. Indications for admission to the pediatric intensive care unit were respiratory failure in 66 (79.5%), neurologic deterioration in six (7.2%), and gastrointestinal symptoms in five (6.0%) patients. Acute lung injury was diagnosed in 23 (27.7%), acute respiratory distress syndrome was diagnosed in 34 (41%), and 51 (61.4%) patients were mechanically ventilated. Oseltamivir was used in 80 (96%) patients. The mortality rate for children with pandemic influenza 2009 was 30.1% compared to an overall mortality rate of 13.7% (p = .0016) among pediatric intensive care unit patients without pandemic influenza during the study period. Also, the mortality rate was 31.7% in patients with comorbidities and 25.0% in previously healthy children (p = .567). The cause of death was primary pandemic influenza infection in 16 (64%), nosocomial infection in four (16%), and primary disease progression in five (20%) patients. The odds ratio for respiratory failure was 14.7 (95% confidence interval, 1.85-111.11), and odds ratio for mechanical ventilation was 27.7 (95% confidence interval, 0.003-200). CONCLUSIONS: Severe disease and high mortality rates were seen in children with pandemic influenza. Death attributable to pandemic influenza occurred in all age groups of children with or without underlying illness. Multiple organ dysfunction syndrome is associated with increased mortality, and death is frequently secondary to severe lung infection caused by pandemic influenza.

Intracranial hemorrhage: clinical and demographic features of patients with late hemorrhagic disease.

BACKGROUND: This retrospective study presents clinical, demographical features and radiological findings as well as outcomes of 31 infants with intracranial hemorrhage (ICH) due to vitamin K deficiency and hence evaluates the risk factors involved. METHODS: Thirty-one cases (17 males and 14 females) having a mean age of 52.52 ± 20.80 days with intracranial hemorrhage due to late hemorrhagic disease of the newborn (LHDN), hospitalized in our clinics were included in the study. Cranial computerized tomography (CT) was performed in all patients for the diagnosis and evaluation of ICH. RESULTS: It was found that the most frequent presenting symptoms were pallor (77.4%), seizures (58%), altered consciousness (58%), vomiting (44%) and poor feeding (35%). Pulsatile fontanel was found in 61% and bulging in 26%. Seven (22.5%) patients had prior history of antibiotic usage. All patients (93.5%) except two were breast fed. Sixteen (51.6%) were delivered at home. Eighteen (58%) had a history of single-dose vitamin K prophylaxis on the first day of delivery. Parenchymal (44%), subdural (39%) or subarachnoidal (22.5%) bleeding was observed. Seven (22.6%) were exitus. During the follow-up period (ranging from 3 months to 18 months) neurological examination findings were recorded. CONCLUSION: Our results indicate that it may be questionable whether single-dose vitamin K prophylaxis at birth is adequate for the prevention of LHDN and if a different timing of this prophylaxis should be made for the exclusively breast fed infants.

Effect of pediatric advanced life support course on pediatric residents' intubation success.

BACKGROUND: The Pediatric Advanced Life Support Program (PALS) course very important for teaching about intubation, resuscitation, shock, trauma, respiratory failure and rhythm disturbances. The aim of the present study was to evaluate the effect of the PALS course on pediatric residents' intubation success during their rotation, daytime and night-time practice in the pediatric intensive care unit (PICU). METHODS: The study was carried out from 1 March 2005 to 28 February 2007. The study period had two parts, in that the number of attempts and successful intubations performed by pediatric residents, and the pediatric intensivist successful intubation ratio were evaluated in two different periods: before the PALS course, 1 March 2005-28 February 2006, and after the PALS course, 5 March 2006-28 February 2007. The participating residents' pediatric levels (PL) were classed as PL-1, PL-2, PL-3, PL-4, and all had first experience in the PICU at the PL-1 level. The PALS instructor was a pediatric emergency or intensive care doctor. We evaluated whether the PALS course influenced intubation success or not. RESULTS: Sixteen residents participated in the study. The proportion of successful intubations was 110 (53.3%) and 104 (65.4%) attempts before and after the PALS course, respectively. The proportion of intubations done by intensivists decreased from 49.1% to 31.7% before and after PALS. The most frequently used endotracheal tube (ETT) internal diameter (ID) was 4.0 mm, and cuffed ETT was used 16% and 21% before and after the course, respectively. Appropriate placing of ETT tip occurred 70.4% and 82.2% of the time before and after the PALS course, respectively. Proportion of successful intubations by residents increased in all levels, except for PL-1. The most important reason for unsuccessful attempts was inappropriate patient position. Only one patient could not be intubated, and laryngeal mask airway was used in that case. During intubation, complications were broken teeth in two patients before the course, and subglottic stenosis developed in only one patient due to cuffed ETT. CONCLUSION: Successful intubation is a life-saving intervention during resuscitation, ETT revision for extubation or obstruction for extubation or obstruction during mechanical ventilation. This skill can be developed in the PALS course and by clinical study in PICU and pediatric emergency services. The PALS course must be given to pediatric residents especially within the first year. Also, cuffed ETT can be used for infants and children.

Diabetic ketoasidosis is associated with prothrombotic tendency in children.

Children and adolescents with type I diabetes mellitus (DM) may present with diabetic ketoacidosis (DKA), which is associated with significant morbidity and mortality. This study aimed to evaluate the hematological parameters at diagnosis (0th hour) and 96th hour after the initiation of treatment in children with DKA. Twenty-six children with DKA treated in Dicle University Faculty of Medicine between September 2002 and August 2003 were included in this study. General characteristics of the patients and hematological parameters (platelet count, white blood cell count, prothrombin time, partial thromboplastin time (PTT), bleeding time, coagulation time, protein C, protein S, antithrombin III, fibrinogen, D-dimer, factor VIII, factor IX, and factor X levels) at diagnosis (0th hour) and 96th hour after the initiation of treatment were determined. The mean age of the children (10 girls and 16 boys) was 9.15 ± 3.85 years (range: 4-15 years). DKA developed for the first time in 58.3% of these children and they had recently been diagnosed as DM. After hematological parameters at 0th hour were evaluated, increased platelet count, decreased PTT, low protein C, and high factor VIII levels were determined at diagnosis, indicating prothrombotic tendency. If the hematological parameters at 0th hour were compared with those at 96th hour; platelet count decreased, PTT increased, protein C and factor VIII levels turned to be normal at 96th hour. When all the results are considered together, children with DKA appeared to have a prothrombotic tendency. Although this tendency was not reflected in clinical findings in this study, it should be kept in mind that children with DKA are prone to the development of thrombosis and they need to be investigated for the possibility of thrombosis.

Antiepileptogenic effects of glutathione against increased brain ADA in PTZ-induced epilepsy.

Adenosine has been shown to play a significant role as a modulator of neuronal activity in convulsive disorders, acting as an endogenous anticonvulsant agent. Any change in adenosine deaminase (ADA) levels will reflect to adenosine levels. In the present study, we have investigated the effect of glutathione on brain tissue ADA levels due to seizures induced by convulsive and subconvulsive dose of pentylenetetrazol (PTZ) in mice. ADA levels due to seizures induced by convulsive and subconvulsive pentylenetetrazol were measured using the Giusti method. ADA levels were higher in the experimental epilepsy groups than in the control and sham groups. ADA levels significantly decreased in the glutathione groups, which may have antiseizure effects. Decreased levels of ADA would be due to increased adenosine levels, protecting against oxidative stress.

Paraoxonase, total antioxidant activity and peroxide levels in marasmic children: relationships with leptin.

OBJECTIVES: The aim of this study was to investigate the oxidant/antioxidant status, paraoxonase (PON) activity and leptin levels in children with marasmic malnutrition. DESIGN AND METHODS: Thirty marasmic children (age 14.4+/-10.3 months) and 28 control subjects were included. Plasma PON activity, total antioxidant activity (TAO), total peroxide (TPX) and leptin levels were measured. RESULTS: Malnourished children had significantly lower leptin (3.6+/-1.1 vs. 11.8+/-4.5 ng/mL, P<0.001), PON activity (66.4+/-28.6 vs. 221.3+/-31.6 IU/L, P<0.001) and TAO (1.44+/-0.12 vs. 2.45+/-0.61 mmol Trolox equiv/L, P<0.001); and higher TPX (15.6+/-6.4 vs. 5.9+/-1.9 micromol/L, P<0.001) values than in controls. Significant negative correlation was found between PON and TPX (P=0.040) and positive correlation between TAO and BMI (P=0.034) in patients. No significant correlation was found between leptin and oxidant/antioxidant parameters (P>0.05). CONCLUSIONS: Children with marasmic malnutrition had increased pro-oxidant and decreased antioxidant status. Extent of oxidative stress increases with malnutrition severity. Antioxidants could be given during nutritional rehabilitation.

The role of nitric oxide in the anticonvulsant effects of pyridoxine on penicillin-induced epileptiform activity in rats.

The present study was conducted to identify the role of nitric oxide (NO) in the anticonvulsant effects of pyridoxine hydrochloride on penicillin-induced epileptiform activity in rats. A single microinjection of penicillin (500 units) into the left sensorimotor cortex induced epileptiform activity within 2-4 min, progressing to full seizure activity lasting about 3-5h. Thirty minutes after penicillin injection, 20, 40, 80, and 160 mg/kg of pyridoxine hydrochloride was administered intraperitoneally (i.p.). Pyridoxine significantly reduced the frequency of penicillin-induced epileptiform activity. A low dose of pyridoxine (40 mg/kg) was the most effective in reducing both the frequency and amplitude of epileptiform activity. The effect of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective N(G)-nitro-L-arginine methyl ester (L-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO substrate, L-arginine on anticonvulsive effects of pyridoxine was investigated. The administration of L-arginine (500 mg/kg, i.p.) and 7-NI (25 and 50 mg/kg, i.p.) significantly decreased the frequency of epileptiform electrocorticographical (ECoG) activity while administration of L-NAME (60 mg/kg, i.p.) and the inactive form of arginine (D-arginine) did not influence it. The administration of L-NAME (60 mg/kg, i.p.) 15 min before pyridoxine (40 mg/kg i.p.) application reversed the anticonvulsant effects of pyridoxine whereas 7-NI (25 and 50 mg/kg, i.p.) did not influence it. The same dose of its inactive enantiomer N(G)-nitro-D-arginine methyl ester (d-NAME) failed to reverse the anticonvulsant effects of pyridoxine. The administration of L-arginine (500 mg/kg, i.p.) did not affect the frequency of epileptiform ECoG activity in the pyridoxine administered group. L-arginine did not reverse the anticonvulsant effect of 7-NI in the penicillin and pyridoxine administered groups. The results of present study indicate that the inhibitory effect on the anticonvulsant activity of pyridoxine against penicillin-induced epileptiform activity was produced by L-NAME, not by 7-NI, and is probably not related to the decrease of NOS activity in the brain.

Hallucination: A rare complication of levetiracetam theraphy.

Levetiracetam is a new antiepileptic drug. In addition to epilepsy, it is also used for treating anxiety disorders and dystonia as well as tardive dyskinesia associated with the use of levodopa and neuroleptic drugs. Phenytoin therapy in a 10-year-old boy with convulsions was discontinued following cardiac rhythm impairment. The patient was then started on levetiracetam. However, visual and auditory hallucinations were observed on the 1st day of levetiracetam therapy. Levetiracetam was discontinued and replaced with sodium valproate, and the hallucinations resolved. The purpose of this report was to remind physicians that hallucinations are one of the rare complications of levetiracetam.

Using terlipressin in a pediatric patient with septic shock resistant to catecholamines.

Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 µg/kg intravenous bolus was administered, followed by a 1 µg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 µg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock.

Hypophosphatemia associated risk factors in pediatric intensive care patients.

San ES, Erdogan S, Bosnak M, San M. Hypophosphatemia associated risk factors in pediatric intensive care patients. Turk J Pediatr 2017; 59: 35-41. The aim of this work is to determine the prevalence and risk factors of hypophosphatemia in pediatric patients admitted to intensive care unit. The study was performed prospectively in patients admitted to the Pediatric Intensive Care Unit between June 2014 and December 2014. Fifty-seven patients were included in the study. The mean age of the study population was 24 months (2-192 months); 25 patients (43.9%) were male and 32 were female (56.1%). The mean body weight z-score was -1.47 ± 2.23, and 23 (40.4%) patients had malnutrition. On admission 16 (28.1%) patients had hypophosphatemia. There were no statistically significant differences between the hypophosphatemic patient group and normophosphatemic patient groups in terms of demographic and clinical characteristics. There were also no significant differences between the two groups in terms of risk factors. Potassium and creatinine levels were significantly lower in the hypophosphatemic group, compared to the normophosphatemic group. According to a multivariate logistic regression analysis, risk factors for hypophosphatemia were low potassium level (OR: 16.76; 95% CI: 2.09 - 134.72; p: 0.008), malignant solid tumors (OR: 52.40; 95% CI: 2.04 - 1,344.32; p: 0.017, p: 0.036). and female gender (OR: 6.18; 95% CI: 1.12 - 34.00; p: 0.036). Prospective studies with larger sample size should be conducted to study the prevalence and risk factors of hypophosphatemia at pediatric intensive care unit.

Comparison of two different regimens of combined interferon-alpha2a and lamivudine therapy in children with chronic hepatitis B infection.

AIM: To evaluate the efficacy of two regimens of combined interferon-alpha2a (IFN-alpha2a) and lamivudine (3TC) therapy in childhood chronic hepatitis B. METHODS: A total of 177 patients received IFN-alpha2a, 9 million units (MU)/m2 for 6 months. In group I (112 patients, 8.7 +/- 3.5 years), 3TC (4 mg/kg/day, max 100 mg) was started simultaneously with IFN-alpha2a, in group II (65 patients, 9.6 +/- 3.8 years) 3TC was started 2 months prior to IFN-alpha2a. 3TC was continued for 6 months after antiHBe seroconversion or stopped at 24 months in nonresponders. RESULTS: Baseline alanine aminotransferase (ALT) was 134.2 +/- 34.1 and 147.0 +/- 45.3; histological activity index (HAI) was 7.4 +/- 2.7 and 7.1 +/- 2.3; and HBV DNA levels were above 2,000 pg/ml in 76% and 66% of patients in groups I and II, respectively (P > 0.005). Complete response was 55.3% and 27.6% in groups I and II, respectively (P < 0.01). AntiHBe seroconversion was higher and earlier, and HBV DNA clearance was earlier in group I (P < 0.05). HBsAg clearance was 12.5% and 4.6% and antiHBs seroconversion was 9.8% and 6.2% in groups I and II, respectively (P > 0.05). Breakthrough occurred in 17.9% and 24.6%; breakthrough times were 15.9 +/- 4.6 and 14.1 +/- 5.1 months; and relapse rates were 6.8% and none in groups I and II, respectively (P > 0.05, P > 0.05, P > 0.05). Responders had higher HAI (HAI > 6) and higher pre-treatment ALT than non-responders. CONCLUSION: Simultaneous 3TC+IFN-alpha2a yields a higher response and earlier antiHBe seroconversion and viral clearance than consecutive combined therapy. Relapse rate is low. Predictors of response are high basal ALT and high HAI scores. 3TC can be administered for 24 months without any side effect and breakthrough rate is comparable with previous studies.

Oxygen therapy via high flow nasal cannula in pediatric intensive care unit.

The aim of the present study was to assess the efficacy and safety of oxygen therapy via high flow nasal cannula in pediatric patients with acute respiratory failure. Patients who were admitted to pediatric intensive care unit and were administered high flow nasal cannula (HFNC) therapy between January 2015 and January 2016 were enrolled. Arterial blood gas parameters, respiratory rates (RR), heart rates (HR), systolic, db > iastolic, and mean arterial pressures (SBP, DBP, MAP), dyspnea scores, fractional oxygen indices (FiO < sub > 2 < /sub > ), and oxygen saturations (SatO < sub > 2 < /sub > ) were recorded at baseline, 30 minutes, and 12 hours. The study enrolled a total of 50 patients of whom 24 (48%) were female and 26 (52%) were male. Statistically significant reductions occurred in mean HR and RR values at 30 minutes and 12 hours compared to those at 0 minute (p < 0.05). Significant increases were observed in SatO2 values at 30 minutes (p.0.001) and 12 hours (p:0.005) compared to SatO2 value at 0 minute (p < 0.05). Similarly, there occurred significant reductions in mean FiO < sub > 2 < /sub > values at 30 minutes and 12 hours compared to baseline (p < 0.05). Significant reductions occurred in mean dyspnea score at 30 minutes (p:0.001) and 12 hours (p:0.001) compared to that at 0 minute (p < 0.05). pH, PaCO < sub > 2 < /sub > , PaO < sub > 2 < /sub > , SBP, and DBP values at 0 minute, 30 minutes, and 12 hours were not significantly different from one another (p > 0.05). No significant correlations were found between treatment failure and age at admission; mean pediatric index of mortality (PIM II), pediatric risk of mortality (PRISM), pediatric logistic organ dysfunction (PELOD) and pediatric multiple organ dysfunction score (P-MODS); and HR, RR, SatO2, pH, PaCO2, PaO2, SBP, DBP, MAP, FiO2 at baseline (p > 0.05). Therapy was successful in 40 (80%) patients whereas there occurred a need for invasive ventilation in 10 (20%) patients. High flow nasal oxygen therapy can be used for patients with acute severe hypoxemic respiratory failure without concurrent hypercapnia when adequate equipment and monitorization tools exist.

Reliability of cerebral oximeter in non-invasive diagnosis and follow-up of hypercapnia.

In this study, aimed to evaluate the sensitivity and specificity of cerebral oximetry and EtCO2 values in non-invasive diagnosis and monitoring of hypercapnia. This study enrolled pediatric patients admitted to and mechanically ventilated at the Pediatric Intensive Care Unit of Gaziantep University Faculty of Medicine Hospital between January 2014 and January 2015. Patients' age, gender, diagnosis, ventilatory parameters, a measured of the mean end-tidal carbon dioxide value stream method, and the simultaneously monitored arterial blood gas PaCO < sub > 2 < /sub > level and near infrared spectroscopy device (NIRS) measurements were recorded. The mean age of patients was 61 months (min 4-max 193), and there were 8 (53.4%) female and 7 (46.6%) male subjects. A significant correlation was found between PCO2 and NIRS, PCO < sub > 2 < /sub > and EtCO < sub > 2 < /sub > (r = 0.571, p < 0.001). There was a significant positive correlation between EtCO2 and NIRS (r = 0.479, p < 0.001). NIRS levels were significantly higher (p < 0.001) in the group with pCO < sub > 2 < /sub > > 45; EtCO < sub > 2 < /sub > > 40 and pH < 7.35, compared to the group with PCO < sub > 2 < /sub > < 45 EtCO < sub > 2 < /sub > < 40 and ph≥7.35 . The best cut-off point for NIRS to distinguish the groups with PCO < sub > 2 < /sub > > 45 with PCO < sub > 2 < /sub > < 45 was 80.5, with a sensitivity of 65.3%, specificity of 84.3%, and positive and negative predictive values of 81.9% and 69.1%, respectively. The best cut-off point for NIRS to distinguish the groups with EtCO < sub > 2 < /sub > > 40 and EtCO < sub > 2 < /sub > < 40 was 81, with a sensitivity of 62.2%, specificity 77.9%, and positive and negative predictive values of 61.2% and 72.3%, respectively. As for pH < 7.35 and PaCO < sub > 2 < /sub > > 45, while sensitivity of EtCO < sub > 2 < /sub > (at a cut-off point of 40) was 64.9%; the sensitivity of NIRS (at a cut-off point of 80.5) was 28.1%, with EtCO < sub > 2 < /sub > being significantly more sensitive than NIRS (p < 0.001). The results of the present study suggest that NIRS values of above 80 should alert clinicians for hypercapnia associated with increased cerebral blood flow.

Respiratuvar depression after accidental nasal ingestion of brimonidine eye drops in infant.

OBJECTIVES: Brimonidine tartrate is an alpha-2 agonist used for glaucoma treatment. It can lead to serious poisoning symptoms when misused by children. CASE REPORT: In this case report, 3 months-old male patient with severe central nervous system depression and respiratory arrest as a result of accidentally nasal instillation of 1 cc brimonidine tartrate that benefited from mechanic ventilation and naloxone treatment was presented. CONCLUSION: This case report suggested, that misuse of nasal brimonidine eye drop could result in serious respiratory distress and central nervous system depression. Mechanical ventilation and naloxone administration can be useful for these patients.

Epileptogenic effects of G protein-coupled estrogen receptor 1 in the rat pentylenetetrazole kindling model of epilepsy.

BACKGROUND: G protein-coupled estrogen receptor 1 (GPER-1) has been demonstrated in several parts of the brain and may play an important role in estrogen downstream signaling pathway. However, the effects of this receptor on epileptic seizure are not clearly known. Therefore, the effects of GPER-1 agonist, G-1, GPER-1 antagonist, G-15 and the main estrogenic hormone, 17ß-estradiol were investigated on seizures and brain tissue oxidative damages induced by pentylenetetrazole (PTZ) in rats. METHODS: In this study, 30 adult male Wistar albino rats were used. Due to intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35mg/kg) which was repeated 12 times every 48h, chemical kindling occurred and kindling seizure was recorded for 30min. The rats were injected with 17ß-estradiol (5µg/kg, ip) or G-1 (5µg/kg, ip), G-15 (5µg/kg, ip), Saline, Ethanol and Dimethyl sulfoxide (DMSO) 30min before each dose of PTZ. Observed seizures were classified between the phase 0-5. Thirty minutes later when the last 12. PTZ administration, all rats were sacrificed and the brain cortex, hippocampus sections were removed and the tissue superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) levels on these tissues were studied. RESULTS: GPER1 agonist, G-1 and estrogenic hormone, 17ß-estradiol significantly increased the development of PTZ kindling the seizures. However, GPER1 antagonist, G-15 did not change the development of PTZ kindling the seizures. In the cortex and hippocampus homogenates, the NO levels after G-1 administration had significantly increased (p<0.05) compared to the PTZ groups but SOD activities and MDA levels demonstrated no difference between the groups. CONCLUSIONS: This is the first study that explores that GPER-1 receptors have epileptogenic effect on PTZ-induced kindling rat. GPER1 may mediate the epileptogenic effect of estrogens by changing the oxidative or anti-oxidative parameters in the brain.

Bone mineral density and cytokine levels during interferon therapy in children with chronic hepatitis B: does interferon therapy prevent from osteoporosis?

BACKGROUND: Our aim was to determinate bone mineral density (BMD), levels of biochemical markers and cytokines in children with chronic hepatitis B treated with interferon (IFN)-alpha and to investigate effect of IFN-alpha therapy on these variables. To the best of our knowledge, this is first study carried out about BMD and cytokine levels in pediatric patients with chronic hepatitis B treated with IFN-alpha. METHODS: BMD, levels of parathyroid hormone (PTH), osteocalcin, C-terminal cross-linking telopeptide of type I collagen (CTX), calcium, alkaline phosphates (ALP), cytokines as TNF-alpha, interleukin (IL)-1beta, IL-2r, IL-6, and IL-8 were studied in 54 children with chronic hepatitis B (4-15 years old) treated with interferon alone (n = 19) or in combination with lamivudine (n = 35) for six months and as controls in 50 age-matched healthy children. RESULTS: There was no significant difference in respect to serum IL-1beta, TNF-alpha and osteocalcin levels while serum IL-2r (p = 0.002), IL-6 (p = 0.001), IL-8 (p = 0.013), PTH (p = 0.029), and CTX (p = 0.021) levels were higher in children with chronic hepatitis B than in healthy controls. BMD of femur neck (p = 0.012) and trochanter (p = 0.046) in patients were higher than in healthy controls. There was a statistically significant correlation between serum IL-1beta and osteocalcin (r = -0.355, p < 0.01); between serum IL-8 and CTX levels (r = 0.372, p = 0.01), and ALP (r = 0.361, p = 0.01); between serum ALP and femur neck BMD (r = 0.303, p = 0.05), and trochanter BMD (r = 0.365, p = 0.01); between spine BMD and IL-2R (r = -0.330, p < 0.05). CONCLUSION: In conclusion, our study suggest that BMD of femur, serum IL-2r, IL-6, IL-8, PTH, and CTX levels were higher in children with chronic hepatitis B treated with IFN-alpha alone or combination with lamivudine than in healthy children. High femur BMD measurements found in patients may suggest that IFN-alpha therapy in children with chronic hepatitis B could contribute indirectly to prevent from hip osteoporosis. Additionally, further investigations on effects of IFN-alpha for bone structure in children should be performed in the future.

The relation between mean platelet volume and mortality in critical pediatric patients.

Mean platelet volume (MPV) is a simple and economical test that is easy to interpret and is routinely measured with automatic cell counters. It indicates platelet volume and platelet function and activation. Variations in platelet volume may occur more as a result of varying differentiation of megakaryocytes in association with production agents in bone marrow rather than of ageing of platelets in circulation. The purpose of this study was to evaluate the relation between mortality and changes in MPV values in patients hospitalized in the pediatric intensive care unit. We evaluated MPV1 levels at the first hour of hospitalization of patients monitored in the pediatric intensive care unit between February 2014 and February 2015, MPV2 levels at the 48th hour, Δ MPV (MPV2-MPV1) values PIM, PRISM, PELOD and PMODS values, diagnosis, age and sex. Fifty-four patients were female (45.4%) and 65 (54.6%) male. The mean age was 51.2 months m(range, 2-189 months). The mean PIM value was 35.4 ± 27.7, the mean PRISM was 18.5 ± 9.3, the mean was PELOD 21.3 ± 10.5, and the mean PMODS was 5.6 ± 3.0. Mortality was correlated with PIM, PRISM, PELOD and PMODS (p<0.001). Sixty-six (55.5%) patients survived. The standardized mortality rate (observed/expected mortality) was 0.99. The mean MPV1 was 9.5 ± 1.05 (range, 6.1-12.4) and mean MPV2 was 9.6 ± 1.15 (range, 6.5-12.5). There was a significant correlation between Δ MPV >0 and mortality (p<0.001). Mortality in patients with Δ MPV ≤0 was 21.4%, but 65.1% in those with levels >0. No correlation was determined between MPV1 and MPV2 and mortality (p= 0.480 and p= 0.213). Δ MPV>0, low levels of albumin and PRISM score were identified as independent risk factors for mortality.

Therapeutic vaccination in the immunotolerant phase of children with chronic hepatitis B infection.

AIM: Hepatitis B virus (HBV) infection is a major global health concern and is the most common cause of chronic liver disease worldwide. Our aim was to investigate the efficacy of specific HBV vaccination as active immunotherapy in treating chronic hepatitis B (CHB) infection during the immunotolerant phase of children with normal aminotransferase values and high viral load. MATERIALS AND METHODS: Seventy-four patients never vaccinated before were randomly and prospectively recruited into two groups. Group 1 included 43 patients vaccinated with three standard injections of the GenHevac B vaccine at 30-day intervals. Group 2 contained 31 patients who did not receive any medication or vaccination (control group). Postvaccination serologic and virologic evaluation was performed 6 months after the first injection and at the end of the 12th month. Response to therapy was defined as loss of HBV DNA in serum and hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg), development of hepatitis B e antibody (anti-HBe). RESULTS: The mean baseline alanine aminotransferase (ALT) value in Group 1 was 33.0 +/- 9.6 IU/l, 34.6 +/- 13.9 IU/l at 6 months after first injection and 34.3 +/- 17.1 IU/l at end of 12 months (P > 0.05). In Group 1 the HBV DNA load at the start of immunization was 3571 +/- 1292 pg/ml; this value was 3220 +/- 1217 pg/ml at the 6th month and 2931 +/- 1292 pg/ml at the 12th month (P > 0.05). In Group 2 the mean ALT values at the beginning of therapy and at the 6th and 12th months were 32.6 +/- 7.8, 32.3 +/- 8.0 and 30.3 +/- 7.3 IU/l, respectively (P > 0.05), and the mean viral load HBV DNA values were 3909 +/- 1378, 3546 +/- 869 and 3106 +/- 718 pg/ml, respectively (P > 0.05). There was no statistically significant difference between Group 1 and Group 2 at the end of the 6th and 12th months in the mean ALT values and mean viral load of HBV DNA (P > 0.05). Except for one patient in each group, hepatitis B surface antigen and HBeAg clearance or hepatitis B surface antibody and anti-HBe seroconversion were not observed during follow-up (P > 0.05). CONCLUSION: In this multicentered study comparison of vaccinated and unvaccinated groups of immunotolerant children with CHB infection showed no difference in the clearance of HBV DNA or seroconversion from HBeAg to anti-HBe. Different immunization protocols should be considered for future investigations in the immunotolerant phase of children with CHB infection.