A Significant Association in Paediatric Emergency Department, Cerebral Sinovenous Thrombosis and Ulcerative Colitis: Review of Literature

ABSTRACT Objective: To discuss cerebral sinovenous thrombosis (CSVT), an important mortality and morbidity factor, developing in the progression of ulcerative colitis (UC) in childhood age, in the light of the literature. Methods: A search of PubMed and Google Scholar database was conducted on April 2014. This study retrospectively investigates the cases diagnosed with UC with complication of CSVT below 18 years of age between years 1971 and 2014. The cases were analysed with respect to age, gender, disease duration and treatment, potential risk factors, clinical findings, location of thrombosis, thrombolytic therapeutical applications, and clinical progressions. Results: Twenty-four paediatric patients aged 5 and 18 years were included in the study. Cerebral sinovenous thrombosis had developed during active disease period in 23 (95.8%) patients. The most common complaints were headache (79.1%) and emesis (29.1%). The most frequently detected risk factors for CSVT were anaemia (58.3%) and thrombocytosis (45.8%). Inherited thrombotic disorders were encountered in 10 (41.6%) of the cases. The most common location sites for CSVT were the transverse (33.3%) and the sigmoid (33.3%) sinuses. It had been discovered that 19 (79.2%) of the cases were healed completely without a sequelae, whereas neurological sequelae remained in three (12.5%) of the cases and two (8.3%) of the cases died. Conclusion: In the presence of a prior diagnosis of UC and emergency presentation with emesis, headache, mood changes and particularly seizure, the presence of CSVT should certainly be considered.

A PATIENT WITH AN ATYPIC NECK MASS LESION.

An 81-year-old woman presented with a history of essential hypertension for eight years and an asymptomatic multinodular goiter that had been incidentally discovered on neck ultrasonography two years ago and an-isohypoechoic mass lesion located adjacent to the right lobe inferior pole of the thyroid gland. Parathyroid adenoma or lymphadenopathy were the differential diagnosis. After two years, the endocrine surgeon decided to operate her multinodular goiter and her probably benign lesion. Intraoperatively, the blood pressure and pulse rate increased markedly and intravenous antihypertensive treatment was administered. She was discharged after blood pressure control. A 2 mm micromedullary thyroid carcinoma with C-cell hyperplasia located on the left lobe of the thyroid was detected. The aforementioned mass lesion was also reported as typical cervical paraganglioma. Because of concomitant medullary thyroid carcinoma with C-cell hyperplasia and paraganglioma the patient was subjected to genetic counseling and molecular testing for hereditary cancer syndromes. A variation of the succinate dehydrogenase gene D (SDHD) NM_003002.3: c.325C> T (Gln109Term) has been reported as the disease-causing mutation. Herein we present a case diagnosed for neck paraganglioma and medullary thyroid carcinoma after an intraoperative hypertensive crisis.

Alzheimer's drug Memantine inhibits metastasis and p-Erk protein expression on 4T1 breast cancer cells.

OBJECTIVES: Drug repurposing studies enable shorter routes to the clinic by skipping the steps like in vitro  in vivo screening, chemical optimization and toxicological studies. In our study, we investigated the potent anti-cancer effect of Alzheimer's drug Memantine on 4T1 breast cancer cells. METHODS: Memantine's effect on proliferation of 4T1 cells was evaluated by using the MTT assay. Memantine inhibited 4T1 cell proliferation in a concentration- dependent manner at 24 and 48 hours. We investigated the drug's effect on the protein expressions of Bax, Bcl-2, Casp-3, Casp-9, E-Cad, Vimentin, B-Cat, GSK3B, p-ERK, ERK, p-GS, GS that are involved in apoptosis, metastasis and cell survival. RESULTS: Memantine altered the Bcl-2, Bax, Casp3, Casp-9 apoptotic protein expression levels. We found that memantine inhibited p-Erk expression and that result suggested a plausible mechanism of action for memantine's antineoplastic effect. Memantine also inhibited wound closure at 24 h, significantly (p = 0.0055). CONCLUSIONS: Memantine inhibited 4T1 breast cancer cell proliferation at significantly lower doses than mostly studied re-purposed drug Metformin. Therefore, we believe that memantine might hold a great promise as a new repositioned drug in cancer treatment and it is our further interest to investigate its effects in vivo (Fig. 3, Ref. 22).

Effect of laser application on microtensile bond strength of an orthodontic adhesive to water-aged composite.

AIM: This study evaluated the microtensile bond strength (MTBS) of an orthodontic adhesive to water-aged composite surfaces using different surface treatments. SUBJECTS AND METHODS: Twelve composite blocks (10 mm × 10 mm × 5 mm) were fabricated and randomly divided into two groups. Half of the specimens were stored in distilled water for 1 day, and the other specimens were stored for 30 days. The specimens were randomly assigned to six groups according to surface treatments (n = 15): Group 1, control (no treatment); Group 2, phosphoric acid; Group 3, diamond bur; Group 4, diamond bur + phosphoric acid; Group 5, laser; and Group 6, laser + phosphoric acid. One coat of orthodontic adhesive was bonded to one surface of composite blocks, and a microhybrid composite resin was bonded to the surfaces via a Teflon mold. Bond strength was evaluated using an MTBS test. Surface topography was evaluated using scanning electron microscopy (SEM) analysis. The data were analyzed using one-way analysis of variance, Tamhane post-hoc test, and independent sample t-tests (P < 0.05). RESULTS: Bond strength values tended to decrease in all groups (with the exception of Group 2) after storage in water for 30 days (P < 0.05). Laser and diamond bur application (with or without phosphoric acid) enhanced the bond strength. CONCLUSIONS: An Er,Cr:YSGG laser application may be a feasible alternative to diamond bur for enhancing the bond strength of orthodontic adhesive to composite resin.

Antimicrobial activity and volatile constituent analysis of three commercial herbal toothpastes containing Aloe vera L. and Fragaria vesca L. extracts.

AIMS: This work was designed to evaluate the antimicrobial activity of three different commercial herbal (Aloe vera L. and Fragaria vesca L. extracts) toothpastes [LR Aloe vera (HTP1), ESI Aloe fresh (HTP2) and ROCS Teens (HTP3)] against two microorganisms that cause tooth infections. MATERIALS AND METHODS: An agar disk diffusion method was used to test the antimicrobial activity of three herbal gel toothpastes in the amount of 100 µL against Streptococcus mutans and Staphylococcus aureus. In the second part of the work, the volatile organic compounds of three different commercial herbal toothpastes (HTP1-3) were determined by solid-phase microextraction/gas chromatography-mass spectrometry-flame ionization detection (SPME/GC-MS-FID). RESULTS: The sensitivity of the tested herbal toothpastes toward each microorganism was expressed as the mean of the clear zone within the range of 6-16 mm diameters. HTP1 and HTP2 were found to be more effective against both bacteria compared with HTP3. Oxygenated monoterpenes (99.34%, 91.44%, and 83.48%) were the most abundant groups in the SPME of HTP1-3, respectively. Menthol (25.41%, 35.82%, and 31.15%) and anethole (52.01%, 23.62%, and 38.79%) were the major compounds identified in the SPME analysis of HTP1-3, respectively. Carvone was found only in HTP3 (0.49%) in a small quantity. CONCLUSION: The commercial herbal toothpastes could have advantages in decreasing bacterial accumulation on teeth with protection of the oral cavity.

Variation in fibroblast expression of toll-like receptor 4 and lipopolysaccharide-induced cytokine production between animals predicts control of bacterial growth but not severity of Escherichia coli mastitis.

Mastitis caused by environmental pathogens such as Escherichia coli is highly problematic to the dairy industry because it incurs substantial cost and tends to be difficult to manage. An effective innate immune response by the host is key to controlling infection, but it should also limit collateral damage to the mammary gland. Between-animal differences in mastitis severity have been attributed to variability in the innate response. In the current study, we used primary dermal fibroblast as a model to rank animals based on composite expression of the toll-like receptor 4 gene (TLR4) and lipopolysaccharide (LPS)-induced IL-8 and IL-6 protein production. Animals ranked as high and low responders (HR and LR, respectively) were then infected with the P4 strain of E. coli to determine how difference in rank would affect response to mastitis. All animals developed an acute response to the infection with varying degrees in severity; however, HR animals had an elevated somatic cell count and fever response at 12 h post-infection and greater production of milk IL-8 at 24 h post-infection. The HR animals were also significantly more capable of limiting bacterial growth. No differences in post-infection milk production or concentrations of milk BSA were measured. The current study indicates that HR animals have an early upregulation in their innate response that is beneficial for bacterial clearance; however, they are equally susceptible to tissue damage caused by an exuberant response to the infection. The dermal fibroblast may be used in conjunction with other cell types to determine how the innate response is regulated to mitigate unnecessary injury to the mammary gland while still effectively clearing the pathogen.

Effects of sodium pyruvate on viability, synthesis of reactive oxygen species, lipid peroxidation and DNA integrity of cryopreserved bovine sperm.

The aim of this study was to examine effects of sodium pyruvate on viability as well as on synthesis of reactive oxygen species (ROS), lipid peroxidation and DNA integrity of cryopreserved bovine sperm. In each of 23 Simmental AI bulls three ejaculates were collected. In a split sample design ejaculates were diluted by using Triladyl® extender without and with the addition of 5mM sodium pyruvate. Both aliquots were equilibrated for 24h before freezing. Frozen sperm samples were thawed, and examined immediately after thawing (0h) as well as after 3, 6, 12, and 24h incubation at 37°C. The percentages of rapidly motile sperm (RMS), plasma membrane and acrosome intact sperm (PMAI), sperm with a high mitochondrial membrane potential (HMMP), amounts of ROS synthesis (dichlorofluorescein-diacetate (DCFH), CellROX Deep Red Reagent® probe (CellROX)) and lipid peroxidation of sperm (LPO) and percentage of sperm with a high degree of DNA fragmentation (%DFI) were determined. Overall, sperm diluted with the extender containing sodium pyruvate showed higher levels of RMS, PMAI and HMMP, CellROX and lower %DFI values (P<0.001) compared to sperm frozen in the extender without sodium pyruvate. However, there was no effect (P>0.05) of sodium pyruvate on LPO and DCFH. The results of this study show that the addition of sodium pyruvate to the semen extender improved the viability as well as DNA integrity of cryopreserved sperm and did not affect their lipid peroxidation, although it increased the synthesis of some ROS.

Managing atypical and typical herpetic central nervous system infections: results of a multinational study.

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

Neonatal lipopolysaccharide exposure does not diminish the innate immune response to a subsequent lipopolysaccharide challenge in Holstein bull calves.

The innate immune response following experimental mastitis is quite variable between individual dairy cattle. An inflammatory response that minimizes collateral damage to the mammary gland while still effectively resolving the infection following pathogen exposure is beneficial to dairy producers. The ability of a lipopolysaccharide (LPS) exposure in early life to generate a low-responding phenotype and thus reduce the inflammatory response to a later-life LPS challenge was investigated in neonatal bull calves. Ten Holstein bull calves were randomly assigned to either an early life LPS (ELL) group (n=5) or an early life saline (ELS) group (n=5). At 7d of age, calves received either LPS or saline, and at 32d of age, all calves were challenged with an intravenous dose of LPS to determine the effect of the early life treatment (LPS or saline) on the immune response generated toward a subsequent LPS challenge. Dermal fibroblast and monocyte-derived macrophage cultures from each calf were established at age 20 and 27d, respectively, to model sustained effects from the early life LPS exposure on gene expression and protein production of components within the LPS response pathway. The ELL calves had greater levels of plasma IL-6 and tumor necrosis factor-α than the ELS calves following the early life LPS or saline treatments. However, levels of these 2 immune markers were similar between ELL and ELS calves when both groups were subsequently challenged with LPS. A comparison of the in vitro LPS responses of the ELL and ELS calves revealed similar patterns of protein production and gene expression following an LPS challenge of both dermal fibroblast and monocyte-derived macrophage cultures established from the treatment groups. Whereas an early life exposure to LPS did not result in a dampened inflammatory response toward a later LPS challenge in these neonatal bull calves, the potential that exposure to inflammation or stress in early life or in utero can create an offspring with a low-responding phenotype as an adult is intriguing and has been documented in rodents. Further work is needed to determine if an inflammatory exposure in utero in a dairy animal would result in a low-responding innate immune phenotype.

Corona mortis: in vivo anatomical knowledge and the risk of injury in totally extraperitoneal inguinal hernia repair.

PURPOSE: Corona mortis (CMOR) is the arterial and/or venous vascular communication(s) between the obturator and external iliac vessels. Totally extraperitoneal (TEP) inguinal hernioplasty can be associated with vascular complications especially during the fixation of the mesh. Theoretically, CMOR is an important nominee. But, the data in literature are insufficient about CMOR injury. Additionally, most of the studies about CMOR have been usually performed on cadavers. We aimed to reveal the preperitoneal vascular anatomy of inguinal area and provide in vivo knowledge about CMOR. The risk of arterial injury was also evaluated. MATERIALS: The data of preperitoneal vascular anatomy of 321 patients who underwent TEP procedure between January 2005 and July 2014 were retrospectively evaluated. RESULTS: Mean age was 46 ± 8.9 years, 53 females vs 268 males. 391 hemipelvises were evaluated. Two types of arterial structure were identified; (1) an aberrant obturator artery forming an anastomosis with branches of ordinary obturator artery; (2) a pubic branch of inferior epigastric artery. The incidence of arterial CMOR was 28.4 % and of any arterial structure was 45.0 %. An arterial CMOR was considered as thick (≥2 mm) or thin (<2 mm). Injury of arterial CMOR during tack stapling on Cooper's ligament was seen in six cases (1.5 %). All of them were thin (<2 mm) in structure. Venous CMOR was visible only under low pressure in work space. CONCLUSION: During TEP hernia repair, CMOR and/or pubic branch of inferior epigastric artery can be damaged. To prevent this complication, tacks should be stapled to Cooper's ligament close to symphysis pubis and dissection should be careful on the posterior surface of superior pubic ramus. Small caliber (<2 mm) arterial CMOR is more prone to be injured during TEP procedure. To explore venous structures properly, pressure in workspace should be kept as low as possible.

Is cystatin-C superior to creatinine in the early diagnosis of contrast-induced nephropathy?: a potential new biomarker for an old complication.

BACKGROUND/AIMS: The aim of this study was to assess whether changes in Cystatin C (CyC) after 48 h post contrast media exposure was a reliable indicator of acute kidney injury and the validity of a risk scoring tool for contrast-induced acute kidney injury (CI-AKI). MATERIALS AND METHODS: We enrolled 121 patients for whom diagnostic coronary angiography were planned. The risk score for CI-AKI was calculated and serum creatinine (sCr) and CyC were measured before and 48 h post coronary angiography. CyC and sCr based AKI was calculated as a 25% increase from baseline within 48 h from contrast media exposure. RESULTS: Mean serum CyC and creatinine concentrations were 0.88 ± 0.27 mg/dL and 0.79 ± 0.22 mg/dL, respectively before the procedure and 1.07 ± 0.47 mg/dL and 0.89 ± 0.36 mg/dL, respectively 48 h after contrast media exposure (P < 0.001). CyC based AKI occurred in 45 patients (37.19 %) and sCr based AKI occurred in 20 patients (16.52%) after the procedure. Mean risk score was found to be 4.00 ± 3.478 and 3.60 ± 4.122 for CyC based AKI and sCr based AKI, respectively and was significantly increased in CyC based AKI group (P < 0.001). CONCLUSIONS: CyC measured 48 h after contrast media exposure may be a more sensitive indicator of CI-AKI relative to creatinine and Mehran risk scoring is in good correlation with CyC increase.

Genotoxicity assessment of vaccine adjuvant squalene.

The genotoxic potential of the vaccine adjuvant Squalene was assessed by the chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and micronucleus (MNs) tests in human lymphocytes and comet assay in both human and rat lymphocytes. Five different concentrations of squalene (1250-20,000 µg/ml for human lymphocytes and 0.07-1.12 mg/kg for rat lymphocytes) were studied. Squalene did not affect the CAs and MN frequency, in all treatments in vitro. A significant increase in SCEs was observed in almost all concentrations at 24 h treatment. Squalene did not affect significantly the comet tail length (CTL) (except 2500 µg/ml) and comet tail intensity (CTI) at all treatments in vitro. In rats, squalene significantly increased and decreased CTL and CTI in some doses. Although there are increasing and reduction in the effect, squalene cannot be regarded as genotoxic in human lymphocytes. However, further in vivo studies are required to be sure on the effect.

Enzyme replacement therapy in an infant with Pompe's disease with severe cardiomyopathy.

Pompe's disease is a glycogen storage disease (type II) characterized by inherited autosomal recessive transmission. A 4 month-old girl presented with rapid disease progression, exhibiting severe hypotonia, and hypertrophic cardiomyopathy, progressing to respiratory failure by the age of 9 months. Despite its low incidence, infantile Pompe's disease is lethal. The availability of an effective treatment has created an urgent need to improve knowledge and early diagnosis of this disease. The clinical response is variable from patient to patient with a better effect in patients enrolled earlier. The only clinically available therapy for Pompe's disease is enzyme replacement therapy (ERT). Gene therapy is still not available for Pompe's disease due to lack of suitable vectors for long-term and tissue-specific expression. Recombinant human alpha-glucosidase remains a hope for patients.

Determination of radioactivity levels and hazards of soil and sediment samples in Firtina Valley (Rize, Turkey).

The natural radioactivity levels in soil and sediment samples of Firtina Valley have been determined. To our knowledge, there seems to be no information about radioactivity level in the Firtina Valley soils and sediments so far. For this reason, soil and sediment samples were collected along the Firtina Valley and analysis on the collected samples were carried out to determine 238U, 232Th, 40K and 137Cs radioisotopes using high purity germanium detector. The activity concentrations obtained for 226Ra, 214Pb, 214Bi, 228Ac, 208Tl, 40K and 137Cs are given in the unit of Bq/kg. The results have been compared with other radioactivity measurements in different country's soils and sediments. The radium equivalent activity (Raeq), the absorbed dose rate (D), the external hazard index (Hex), the annual gonadal dose equivalent (AGDE) and the annual effective dose equivalent (AEDE) were also calculated and compared with the international recommended values.

Prediction of difficult tracheal intubation in Turkish patients: a multi-center methodological study.

BACKGROUND AND OBJECTIVE: Preoperative evaluation is important in the detection of patients at risk for difficult airway management. It is still unclear whether true prediction is possible and which variables should be chosen for evaluation. The aim of this prospective, multi-centre study was to investigate the incidence of difficult intubation, the sensitivity and positive predictive values of clinical screening tests and whether combining two or more of these tests will improve the prediction of difficult intubation in Turkish patients. METHODS: Seven study sites from six regions in Turkey participated in this study. One thousand six hundred and seventy-four ASA physical status I-III patients, scheduled to undergo elective surgery under general anaesthesia, were included. RESULTS: The incidence of difficult intubation was 4.8% and increased with age (P < 0.05). The incidence of difficult intubation was significantly higher in patients who had a Mallampati III or IV score, a decreased average thyromental and sternomental distance, decreased mouth opening, or decreased protrusion of the mandible (P < 0.05). Mouth opening and Mallampati III-IV were found to be the most sensitive criteria when used alone (43% and 35%, respectively). Combination of tests did not improve these results. CONCLUSIONS: There is still no individual test or a combination of tests that predict difficult intubations accurately. Tests with higher specificity despite low positive predictive value are needed.

Clonidine addition prolongs the duration of caudal analgesia.

BACKGROUND: In this study, using a dose-ranging design, we examined the effects of clonidine with 0.125% bupivacaine on the duration of post-operative analgesia in caudal anaesthesia in children. METHODS: We conducted a controlled, prospective study of clonidine in caudal anaesthesia in 60 children, aged 1-10 years, undergoing elective inguinal hernia repair. Induction and maintenance of anaesthesia were performed by inhalation of sevoflurane and nitrous oxide. The children were randomized in a double-blind fashion to four groups, and were given a caudal anaesthetic with either 0.125% plain isobaric bupivacaine (1 ml/kg) or bupivacaine plus 1, 1.5 or 2 microg/kg of clonidine. The blood pressure and heart rate were recorded peri-operatively. Analgesia was evaluated by the modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS) or a visual analogue scale (VAS). Paracetamol was given when the mCHEOPS score was greater than five or when the VAS score was greater than 30 mm. The monitoring of scores for pain, haemodynamic changes and post-operative nausea and vomiting was performed by nurses blind to the study allocation. RESULTS: The duration of analgesia was found to be significantly longer in the group given bupivacaine plus 2 microg/kg of clonidine (median, 650 min; range, 300-900 min). Peri-operative hypotension and bradycardia, post-operative respiratory depression and motor block were not recorded in any patient. CONCLUSIONS: The addition of clonidine to 0.125% bupivacaine prolongs the duration of post-operative analgesia without any respiratory or haemodynamic side-effects.

Determination of tetrahydrozoline hydrochloride and fluorometholone in pharmaceutical formulations by HPLC and derivative UV spectrophotometry.

Two methods for the quantitative determination of tetrahydrozoline hydrochloride (1) and fluorometholone (2) in pharmaceutical eye drops (Efemoline) are described. The procedures are based on derivative UV spectrophotometry and HPLC. In the former method, d2A/d lambda 2 values were measured in methanol at 226 and 282 nm for 1 and 2, respectively. The relative standard deviations for the method were found to be 1.06% for 1 and 0.98% for 2. The latter method based on a reversed phase HPLC system using a Partisil 5 ODS analytical column. The mobile phase used for the separation of 1, 2 and internal standard (lidocaine) was methanol/acetonitrile/water (50:50:10 v/v) and the compounds in the eye drops were detected at 220 nm using an UV detector. The relative standard deviations for the HPLC method were determined to be 0.61% and 0.50% for 1 and 2, respectively. The proposed methods, which give thoroughly comparable data, are simple, rapid, and allow precise and accurate results and could be used for commercial formulations containing tetrahydrozoline hydrochloride and fluorometholone in combination.