Transient Abnormalities Research Articles

Assessment of incidence, determinants and co-morbidities associated with meconium aspiration syndrome: a hospital based study

Background: Meconium aspiration syndrome (MAS) was found to be major contributing factor towards perinatal morbidity and mortality. This condition is mainly accompanied with respiratory failure, pulmonary air leaks and pulmonary hypertension in neonates. A conservative approach of obstetrician-paediatrician combination moderates incidence of MAS and its complications. The objective of the study was to determine the incidence, determinants and co-morbidities associated with MAS in both intramural and out born admitted to the NICU and SNICU of a Chandulal Chandrakar memorial hospital located in Bhilai, Chattisgarh, India. Methods: This was a prospective study conducted in Chandulal Chandrakar memorial hospital, Bhilai from 1 st September 2013 to 31 st February 2015, in newborns with history of meconium stained amniotic fluid (MSAF) in both out-born and inborn units. Neonates who met inclusion criteria they were included in the study. The data were recorded in predesigned proforma. The data was analyzed using Chi square test. Level of significance of this data was set at p <0.05 . Results: Incidence of MSAF in the in-born and out-born among all children admitted was 52.4% and 47.5% respectively. Out of total 202 subjects of MSAF, those with MAS were 29.7% and of these 75% were inborn and 25% were out-born. Male preponderance was high in the study compared to female babies. Incidence of MAS was significantly more in children of >2.5 kgs (80%) and common in primiparous mothers (60%) with lower segmental caesarian sections. MAS commonly seen in post -term babies (53.33%) than those of term (36.66%) or pre-term (10%) gestation. Fetal distress was the common complication observed in most of the cases (91.1%) and one death related to this was noted. At the end of 1 year there were predominantly more children (40%) who developed respiratory morbidities. Delayed development was seen among 13.3% children and transient tone abnormalities were noted in about 2% of infants. Conclusions: The overall incidence of MAS was found to have been 30% among cases of MSAF, which was relatively higher due to delayed referral. This percentage could have been reduced along with associated co-morbidities with appropriate antenatal check-up’s and timely referral.

Bile Duct Injury after Irreversible Electroporation of Hepatic Malignancies: Evaluation of MR Imaging Findings and Laboratory Values

PurposeTo evaluate biliary complications after irreversible electroporation (IRE) of hepatic malignancies. Materials and MethodsIn 24 patients (17 men; mean age, 59.3 y), bile ducts were located within a 1.0-cm radius of the ablation zone at subacute follow-up (ie, 1–3 d) after percutaneous IRE of 53 hepatic tumors (primary hepatic tumors, n = 14). MR imaging, conducted with a hepatocyte-specific contrast agent before and after treatment, was examined for evidence of bile duct injury. Serum bilirubin and alkaline phosphatase levels measured at subacute and short-term follow-up (ie, 1–2 mo after IRE) were analyzed for evidence of biliary injury. Correlations between bile duct injury and characteristics of patients, lesions, and ablation procedures were assessed by generalized linear models. ResultsFifty-five bile ducts were located within 1.0 cm of an ablation defect. Locations relative to the ablation area were as follows: 33 were encased, 14 were abutting, and 8 were located within a radius of 0.1–1.0 cm of the ablation zone. Subacute follow-up MR images showed 15 bile duct injuries (narrowing, n = 8; dilation, n = 7). At subacute follow-up, three patients showed transient abnormalities of laboratory values (bilirubin, 1.6–5.2 mg/dL). Short-term laboratory values were abnormal in one patient (increase in alkaline phosphatase of 533 U/L vs baseline) as a result of local tumor recurrence. Patient age (continuous, P = .026; < 65 y vs ≥ 65 y, P = .001) was independently associated with post-IRE bile duct injury. ConclusionsBile ducts adjacent to an IRE ablation area remain largely unaffected by this procedure.

Levodopa-responsive Holmes' Tremor Caused by a Single Inflammatory Demyelinating Lesion.

BackgroundHolmes’ tremor is characterized by a combination of rest, postural, and kinetic tremor that is presumably caused by interruption of cerebello-thalamo-cortical and nigrostriatal pathways. Medical treatment remains unsatisfactory.Case ReportA 16-year-old girl presented with Holmes’ tremor caused by a transient midbrain abnormality on magnetic resonance imaging (MRI). To explore the discrepancy between persistent tremor and resolved MRI changes, we performed dopamine transporter single-photon emission computed tomography (DaT-SPECT) with a 123I-ioflupane that revealed nearly absent DaT binding in the right striatum. Levodopa dramatically improved the tremor.DiscussionThis is only the second report of a transient midbrain MRI abnormality disrupting nigrostriatal pathways. The case highlights the sometimes limited sensitivity of morphologic imaging for identifying the functional consequences of tissue damage and confirms that DaT imaging may serve as a predictor for levodopa responsiveness in Holmes’ tremor.

Levodopa-responsive Holmes’ Tremor Caused by a Single Inflammatory Demyelinating Lesion

<strong>Background:</strong> Holmes’ tremor is characterized by a combination of rest, postural, and kinetic tremor that is presumably caused by interruption of cerebellothalamo-cortical and nigrostriatal pathways. Medical treatment remains unsatisfactory. <strong>Case Report:</strong> A 16-year-old girl presented with Holmes’ tremor caused by a transient midbrain abnormality on magnetic resonance imaging (MRI). To explore the discrepancy between persistent tremor and resolved MRI changes, we performed dopamine transporter single-photon emission computed tomography (DaTSPECT) with a 123I-ioflupane that revealed nearly absent DaT binding in the right striatum. Levodopa dramatically improved the tremor. <strong>Discussion:</strong> This is only the second report of a transient midbrain MRI abnormality disrupting nigrostriatal pathways. The case highlights the sometimes limited sensitivity of morphologic imaging for identifying the functional consequences of tissue damage and confirms that DaT imaging may serve as a predictor for levodopa responsiveness in Holmes’ tremor.

Interest of neuromotor assessment in early screening of children at high risk for cerebral palsy within a specialized network

To identify clinical and laboratory signs of early screening of cerebral palsy in order to propose an early management of children. Prospective study including 100 newborns with risk factors for CP (relying on gestational age, birth weight, perinatal and neonatal brain injuries). The screening was conducted during a medical consultation by a specialist and was based on clinical setting (neurological examination and neuromotor assessment) and radiological examination (cranial ultrasound, magnetic resonance imaging). The clinical assessment was performed at the 1st, 4th, 9th, 12th, 18th, 24th months and at 5 years after selection of patients. The different clinical factors were weak predictors of becoming during the first month of life. At 4 months, the factors correlated with the evolution to cerebral palsy were: the decrease of lower limbs’ spontaneous movements and the lower limb fixed in extension at suspension maneuvers ( P < 0.001), Babinski sign ( P < 0.001), as well as absence of an ulnar-palmar grip ( P < 0.01). At 9 months, we found more predictive signs of the evolution to CP, particularly the head holding problems ( P < 0.001), the absence of acquisition of sitting position ( P < 0.001), the absence of precision grip ( P < 0.001), the deficit of uprising the lower limbs, of hip abduction, of extension of the knee in the lateral inclinations and drawn-seated ( P < 0.001), hyperreflexia ( P = 0.004) and the Babinski sign ( P < 0.001). At 12, 15 and 18 months, neurological examination showed a peripheral hypertonia in 62% of children. At 24 months, peripheral hypertonia is found only in 43% of cases. 38% of children had an adequate level of psychomotor development and a normal neurological examination hence the diagnosis of transient motor abnormalities (TMA) was retained. For imaging, normal cranial ultrasound was significantly more associated with TMA than CP ( P < 0.001). Neurological examination focusing on reflexes and muscle tone is poorly predictive in the first months of life. Neuromotor assessment with the study of spontaneous movements may reflect functional limitations in the first months of life and have been shown to predict later CP. However, the distinction between CP and TMA remains difficult and requires a long follow-up.

Transient isolated ocular motor abnormality related to perilesional edema of an acute medullary microbleed: A case report and review of the literatures

We report a case of transient isolated gaze-evoked nystagmus with ocular lateropulsion in a patient with an acute medullary microbleed which was detected by brain magnetic resonance imaging. Considering the correlation between the neural structures involved by the lesion and the ocular motor symptoms of this patient, we suggest that the perilesional edema of the acute medullary microbleed is responsible for this transient ocular motor abnormality.

Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes.

Comprehensive functioning of Ca2+ cycling is crucial for excitation–contraction coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs.

Functional lower lip reconstruction with the modified Bernard–Webster flap

Lower lip defects after squamous cell carcinoma (SCC) excisions have been repaired by several surgical techniques. However, the functional reconstruction of full-thickness defects of the lower lip remains a therapeutic challenge. We therefore evaluated functional results of the modified Bernard-Webster flap for the reconstruction of full-thickness lower lip defects after SCC excisions. A prospective study was performed on all patients with lower lip full-thickness defects after SCC excisions greater than 1/3 of the lip, reconstructed with the modified Bernard-Webster flap in 2011-2013. Functional (sphincter, motor, and sensory functions) postoperative results were evaluated according to criteria previously adopted. Twelve lower lip defects were reconstructed without complications, except for two (16.7%) wound dehiscence successfully managed. Ten (83.3%) patients presented transient and permanent functional abnormalities in the recent and late postoperative assessments. Ten (83.3%) patients classified the late functional results as satisfactory. The modified Bernard-Webster flap proved to be an excellent alternative to repair full-thickness lower lip defects with more than 1/3 of the lower lip length, as it allowed the use of similar neighboring tissues, could be performed in one stage, and was functionally effective.

Intrinsic brain activity as a diagnostic biomarker in children with benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting-state functional magnetic resonance imaging (RS-fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age-matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS-fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp 36:3878-3889, 2015. © 2015 Wiley Periodicals, Inc.

PTH-053 Inflammatory bowel disease and liver function disturbance: literature review and retrospective study of 574 patients

<h3>Introduction</h3> Abnormal liver function tests (LFTs) are present in up to 40% of patients with Inflammatory Bowel Disease (IBD). These abnormalities are often transient. A few studies in the current literature suggest that transient disturbances may be related to disease activity,^1,2whilst others have failed to find a causal association.³The aim of this study is to identify the link between abnormal LFTs and IBD activity. <h3>Method</h3> Literature review was performed using Pubmed. For the retrospective study, patients with Ulcerative Colitis (UC) and Crohn’s disease (CD) who were admitted to our institution in 2013 were identified. Patient’s electronic records were used. Exclusion criteria: less than 16 years old, LFTs documented for less than 12 months or on less than 3 occasions. Abnormalites were defined as ’transient’ if at least one of: alanine transaminase, alkaline phosphatase or bilirubin was disturbed for less than 4 weeks or ‘persistent’ if disturbed for more than 4 weeks. <h3>Results</h3> 8 studies were included in the literature review. There was significant heterogeneity in the frequency of abnormal LFT (3%⁴to 40%²) due to variations in the definitions used. Our study included 264 CD patients and 310 UC patients who were followed for a median of 34 months. Abnormal LFTs were found in 242/574 (42%) patients. 66% of abnormalities were transient and 34% were persistent. The causes identified for 192 patients with transient abnormalities were: 70 IBD flare, 52 antibiotics/infection, 3 thiopurine drugs, 59 unknown, 3 fatty liver, 5 other. The causes identified for 99 patients with persistent abnormalities were: 22 IBD flare, 14 infections, 12 PSC, 18 unknown cause, 5 fatty liver, 4 Gilberts, 5 thiopurine drugs, 3 pregnant, 16 other. <h3>Conclusion</h3> This study lends support to the notion that an IBD flare can cause deranged LFTs independently of thiopurine drugs. Mild abnormalities during a flare can be monitored. Further investigations are warranted if the bilirubin is raised or if the LFTs are markedly deranged or persist more than 4 weeks after resolution of the flare. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Broome U, Glaumann H, Hellers G, Nilsson B, Sorstad J, Hultcrantz R. Liver disease in ulcerative colitis: an epidemiological and follow up study in the country of Stockholm. Gut. 1994;35(1):84–89 Yamamoto-Furusho JK, Sanchez-Osorio M, Uribe M. Prevalence and factors associated with the presence of abnormal liver function tests in patients with ulcerative colitis. Ann Hepatol. 2010;9(4):397–401 Mendes FD, Levy C, Enders FB, Loftus EV, Angulo P, Lindor KD. Abnormal hepatic biochemistries in patients with inflammatory bowel disease. <i>Am J Gastroenterol. </i>2007;102:344–350 Shepherd HA, Selby WS, Chapman RW, Nolan D, Barbatis C, McGee JO, Jewell DP. Ulcerative colitis and persistent liver dysfunction. Q J Med.1983;52(208):503–13

Murine Inhibin α-Subunit Haploinsufficiency Causes Transient Abnormalities in Prepubertal Testis Development Followed by Adult Testicular Decline.

Activin production and signaling must be strictly regulated for normal testis development and function. Inhibins are potent activin inhibitors; mice lacking the inhibin-α gene (Inha-/- mice) cannot make inhibin and consequently have highly elevated activin and FSH serum concentrations and excessive activin signaling, resulting in somatic gonadal tumors and infertility. Dose-dependent effects of activin in testicular biology have been widely reported; hence, we hypothesized that male mice lacking one copy of the Inha gene would produce less inhibin and have an abnormal reproductive phenotype. To test this, we compared hormone concentrations, testis development, and sperm production in Inha+/+ and Inha+/- mice. Serum and testicular inhibin-α concentrations in adult Inha+/- mice were approximately 33% lower than wild type, whereas activin A, activin B, FSH, LH, and T were normal. Sixteen-day-old Inha+/- mice had a mixed phenotype, with tubules containing extensive germ cell depletion juxtaposed to tubules with advanced Sertoli and germ cell development. This abnormal phenotype resolved by day 28. By 8 weeks, Inha+/- testes were 11% larger than wild type and supported 44% greater daily sperm production. By 26 weeks of age, Inha+/- testes had distinct abnormalities. Although still fertile, Inha+/- mice had a 27% reduction in spermatogenic efficiency, a greater proportion of S-phase Sertoli cells and lower Leydig cell CYP11A1 expression. This study is the first to identify an intratesticular role for inhibin/inhibin-α subunit, demonstrating that a threshold level of this protein is required for normal testis development and to sustain adult somatic testicular cell function.

Early school outcomes for extremely preterm infants with transient neurological abnormalities.

To determine if transient neurological abnormalities (TNA) at 9 months corrected age predict cognitive, behavioral, and motor outcomes at 6 years of age in extremely preterm infants. A cohort of 124 extremely preterm infants (mean gestational age 25.5wks; 55 males, 69 females), admitted to our unit between 2001 and 2003, were classified based on the Amiel-Tison Neurological Assessment at 9 months and 20 months corrected age as having TNA (n=17), normal neurological assessment (n=89), or neurologically abnormal assessment (n=18). The children were assessed at a mean age of 5 years 11 months (SD 4mo) on cognition, academic achievement, motor ability, and behavior. Compared with children with a normal neurological assessment, children with TNA had higher postnatal exposure to steroids (35% vs 9%) and lower adjusted mean scores on spatial relations (84 [standard error {SE} 5] vs 98 [SE 2]), visual matching (79 [SE 5] vs 91 [SE 2]), letter-word identification (97 [SE 4] vs 108 [SE 1]), and spelling (76 [SE 4] vs 96 [SE 2]) (all p<0.05). Despite a normalized neurological assessment, extremely preterm children with a history TNA are at higher risk for lower cognitive and academic skills than those with normal neurological findings during their first year of school.

Early panretinal abnormalities on fundus autofluorescence and spectral domain optical coherence tomography after intravitreal ocriplasmin

Intravitreal ocriplasmin, a recombinant truncated form of plasmin with proteolytic activity against laminin and fibronectin (Hermel et al. 2010), has recently been approved as treatment strategy for vitreomacular traction (VMT). However, concerns have been raised regarding its ocular safety (Kim 2014). Clinical trials reported adverse events that included transient visual loss, dyschromatopsia and photopsias, usually associated with decreased amplitudes on electroretinography (ERG) (Stalmans et al. 2012). Spectral domain optical coherence tomography (SD-OCT) abnormalities have been detected within the macula, and ERG studies have demonstrated diffuse retinal dysfunction related to presumed ocriplasmin toxicity (Fahim et al. 2014; Tibbetts et al. 2014). Herein, we demonstrate that early structural abnormalities to the photoreceptors as detected by fundus autofluorescence (FAF) and SD-OCT may affect not only the macula but also the peripheral retina as well. A 69-year-old woman presented with visual acuity of 20/32 and metamorphopsia in her right eye. Fundus examination and SD-OCT revealed VMT with small detachment of the foveal cones; FAF was normal (Fig. 1A,E). The day after uneventful intravitreal ocriplasmin (0.125 mg/0.1 ml), her vision decreased to 20/50 and she complained of dyschromatopsia. SD-OCT demonstrated the appearance of subfoveal fluid and multifocal shallow subretinal detachments (Fig. 1J–L), as well as focal areas of attenuation/thinning of the ellipsoid zone line and disappearance of the interdigitation zone line of the photoreceptors. Photoreceptor abnormalities corresponded to patchy areas of abnormally increased FAF signal within the macula (Fig. 1B,F) as well as to radial lines of abnormally increased FAF signal towards the retinal periphery (Fig. 1I). At day 7, her vision improved to 20/40 and dyschromatopsia was resolved. SD-OCT demonstrated the released VMT, decreased subfoveal fluid and shaggy photoreceptors in the fovea (Fig. 1C,G). Persisting attenuation/thinning of the ellipsoid zone line and further disappearance of the interdigitation zone line were noted. After 4 months, FAF and SD-OCT abnormalities disappeared completely (Fig. 1D,H). Clinical trials that compared intravitreal ocriplasmin to placebo in treatment of VMT indicated that visual symptoms were greater in patients receiving ocriplasmin (Stalmans et al. 2012). In addition, decreased amplitudes in all ERG variables were noted, indicating the presence of panretinal dysfunction that persisted for several months (Fahim et al. 2014; Tibbetts et al. 2014). Our imaging study supports these functional findings; indeed, structural damage to the photoreceptors was not confined within the macula, but was actually widespread throughout the periphery. These abnormalities may be due to a protease effect on laminin, which is present not only in the vitreous but also throughout the retina, including the interphotoreceptor matrix (IPM) (Fahim et al. 2014). Interestingly, in our case, there was greater and broader damage to the interdigitation zone line compared to the ellipsoid zone line. Normal reflectivity of the interdigitation zone line arises from well-oriented and aligned interdigitations of apical processes of the retinal pigment epithelium (RPE) with outer segments of the photoreceptors. We hypothesize that lysis of the IPM caused by ocriplasmin may create a loss of the normal alignment between photoreceptors and RPE microvilli, therefore causing reduced reflectivity of the interdigitation zone line. In addition, given the pivotal role of a healthy IPM for maintaining adhesion between retina and RPE, lysis of the IPM may reduce strength of the adhesion and thus cause multifocal detachments of the retina in areas where vitreoretinal traction was not significant. In summary, although ocriplasmin is effective in releasing VMT, presumed toxic effects of the drug may lead to visual disturbances as well as to early but transient panretinal structural abnormalities, especially involving the interdigitation zone. We suggest evaluating carefully the retinal periphery after ocriplasmin injection to detect any possible toxicity for the photoreceptors. Given the limited follow-up of patients who experienced presumed ocriplasmin toxicity, further research is needed to investigate risk factors, duration of recovery and ways to prevent or minimize toxic effects of the drug.

Effects of rhinovirus infection of pulmonary function of healthy human volunteers.

The effects of experimentally induced rhinovirus and mycoplasmal respiratory tract infections on the pulmonary function of healthy, young, adult volunteers were investigated prospectively. Before inoculation, 12 volunteers were completely normal, whereas 9 had increased frequency dependence of compliance as their only abnormality of pulmonary function. Rhinovirus infection was induced in 8 of the completely normal volunteers, and 5 developed increased frequency dependence of compliance at the time of illness. These changes returned toward normal during the following 2 weeks and were not associated with concomitant changes in any other parameter of pulmonary function, including "closing volume". Three subjects with increased frequency dependence of compliance as their only abnormality before rhinovirus infection developed no significant change in dynamic compliance or any other abnormality in pulmonary function after infection. No changes in pulmonary function were detected in 3 volunteers with experimentally induced mycoplasmal infection. These finding suggest that although rhinovirus infections are associated primarily with upper respiratory illness, they can produce transient peripheral airway abnormalities in previously normal young adults; however, closing volumes, as well as routine pulmonary function studies, may not detect these changes.

Activating enhancer binding protein 2 epsilon (AP-2ε)-deficient mice exhibit increased matrix metalloproteinase 13 expression and progressive osteoarthritis development.

IntroductionThe transcription factor activating enhancer binding protein 2 epsilon (AP-2ε) was recently shown to be expressed during chondrogenesis as well as in articular chondrocytes of humans and mice. Furthermore, expression of AP-2ε was found to be upregulated in affected cartilage of patients with osteoarthritis (OA). Despite these findings, adult mice deficient for AP-2ε (Tfap2e−/−) do not exhibit an obviously abnormal cartilaginous phenotype. We therefore analyzed embryogenesis of Tfap2e−/− mice to elucidate potential transient abnormalities that provide information on the influence of AP-2ε on skeletal development. In a second part, we aimed to define potential influences of AP-2ε on articular cartilage function and gene expression, as well as on OA progression, in adult mice.MethodsMurine embryonic development was accessed via in situ hybridization, measurement of skeletal parameters and micromass differentiation of mesenchymal cells. To reveal discrepancies in articular cartilage of adult wild-type (WT) and Tfap2e−/− mice, light and electron microscopy, in vitro culture of cartilage explants, and quantification of gene expression via real-time PCR were performed. OA was induced via surgical destabilization of the medial meniscus in both genotypes, and disease progression was monitored on histological and molecular levels.ResultsOnly minor differences between WT and embryos deficient for AP-2ε were observed, suggesting that redundancy mechanisms effectively compensate for the loss of AP-2ε during skeletal development. Surprisingly, though, we found matrix metalloproteinase 13 (Mmp13), a major mediator of cartilage destruction, to be significantly upregulated in articular cartilage of adult Tfap2e−/− mice. This finding was further confirmed by increased Mmp13 activity and extracellular matrix degradation in Tfap2e−/− cartilage explants. OA progression was significantly enhanced in the Tfap2e−/− mice, which provided evidence for in vivo relevance. This finding is most likely attributable to the increased basal Mmp13 expression level in Tfap2e−/− articular chondrocytes that results in a significantly higher total Mmp13 expression rate during OA as compared with the WT.ConclusionsWe reveal a novel role of AP-2ε in the regulation of gene expression in articular chondrocytes, as well as in OA development, through modulation of Mmp13 expression and activity.

Neurogenic stress cardiomyopathy associated with subarachnoid hemorrhage.

Cardiac manifestations are recognized complications of subarachnoid hemorrhage. Neurogenic stress cardiomyopathy is one complication that is seen in acute subarachnoid hemorrhage. It can present as transient diffuse left ventricular dysfunction or as transient regional wall motion abnormalities. It occurs more frequently with neurologically severe-grade subarachnoid hemorrhage and is associated with increased morbidity and poor clinical outcomes. Managing this subset of patients is challenging. Early identification followed by a multidisciplinary team approach can potentially improve outcomes.

Clinical and laboratory characteristics of neonatal hypocalcemia.

PurposeTo describe the clinical characteristics of full-term neonates with hypocalcemia and to suggest factors associated with neonatal hypocalcemiaMethodsThe medical records of full-term neonates with hypocalcemia were reviewed. Hypocalcemia was defined as an ionized calcium (iCa) concentration of <4 mg/dL. Parathyroid hormone (PTH) insufficiency was defined as a serum PTH level of <60 pg/mL or a serum phosphorus level higher than the serum calcium level in the presence of hypocalcemia.ResultsFifty-three neonates were enrolled. The median age at diagnosis of hypocalcemia was 3 days. In all the neonates, formula feeding predominance was observed. Thirty-eight neonates (69.8%) were compatible with PTH insufficiency. The number of formula-fed neonates was significantly higher than that of breast-fed patients among neonates with PTH insufficiency (P=0.017). Intact PTH was negatively correlated with serum phosphorus levels. Twelve out of 14 neonates (85.7%) had 25-hydroxy vitamin D (25OHD) levels <20 ng/mL and 9 neonates (64.3%) had 25OHD levels <10 ng/mL. Twenty-one neonates had hypocalcemic tetany. The serum calcium and iCa concentrations of neonates with tetany were 4.2-8.3 mg/dL and 1.85-3.88 mg/dL, respectively. Three neonates showed symptomatic hypocalcemia with calcium levels over 7.5 mg/dL. Among the 16 neonates who underwent electroencephalography (EEG), 12 had abnormalities, which normalized after 1-2 months.ConclusionFormula milk feeding, PTH insufficiency and low serum vitamin D concentration are associated with the development of neonatal hypocalcemia. Symptoms such as tetany and QT interval prolongation can develop in relatively mild hypocalcemia. Moreover, transient neonatal hypocalcemia can cause transient EEG abnormalities.

Echocardiologic evaluation and follow-up of cardiovascular complications in children with scorpion sting in coastal South India

Introduction and Objective:Scorpion stings are a common emergency in India and many other tropical countries. In India, the red scorpions are more prevalent, and their venom is more likely to cause myocardial dysfunctions. There are very few studies conducted on this problem. The following study was done in Andhra Pradesh and aimed to identify cardiovascular complications of scorpion stings in children with a follow-up of 6 monthsStudy Design:Prospective observational study.Setting:Children admitted with scorpion sting in a tertiary care hospital between December 2009 and November 2010 and followed-up till May 2011.Results:Scorpion stings account for 1 in every 36 admissions. Maximum cases were in 0–3 years age group. Electrocardiogram changes were seen in 76% cases and myocarditis in 42% cases. Echocardiography revealed decreased ejection fraction (EF), transient mitral regurgitation and wall motion abnormalities were observed. Average EF improved from 16% on day 1 to 47.94% and 59% on day 5 and 14 respectively, which was highly statistically significant. By the end of 1 month, all the survivors had normal EF and no residual cardiac dysfunction was observed at 6 months.Conclusion:Scorpion stings, a common and fatal medical emergency in India, produce echocardiographic changes without any long term residual damage on myocardial activity.

Study the Changes of Thyroid Hormones Levels Following Major Urological Surgery

This study was designed to evaluate the effect of major surgery on thyroid hormones and thyrotropin in patient undergoing major lower abdominal surgery. The study included fifty patients scheduled for elective major lower abdominal surgery, the serum levels of T3, T4 and TSH were determined one day preoperatively, intraoperative, one day postoperatively, two days postoperatively, and rT3 was determined one day preoperatively, and one day postoperatively. We observed that the levels of (T3, T4, TSH) increased significantly (P0.05). rT3 increased not significant (P&gt;0.05) in one day postoperatively. It has been proposed these changes due to surgical stress that inhibits peripheral conversion of T4 to T3 by inhibiting peripheral 5'-deiodinase activity, also The absence of pituitary response to changes in serum levels of T3 and T4.According to the results of this study there is a transient abnormality in thyroid function tests in patient undergoing elective major surgery and this abnormality due to surgical stress.

Study the Changes of Thyroid Hormones Levels Following Major Urological Surgery

This study was designed to evaluate the effect of major surgery on thyroid hormones and thyrotropin in patient undergoing major lower abdominal surgery. The study included fifty patients scheduled for elective major lower abdominal surgery, the serum levels of T3, T4 and TSH were determined one day preoperatively, intraoperative, one day postoperatively, two days postoperatively, and rT3 was determined one day preoperatively, and one day postoperatively. We observed that the levels of (T3, T4, TSH) increased significantly (P0.05). rT3 increased not significant (P&gt;0.05) in one day postoperatively. It has been proposed these changes due to surgical stress that inhibits peripheral conversion of T4 to T3 by inhibiting peripheral 5'-deiodinase activity, also The absence of pituitary response to changes in serum levels of T3 and T4.According to the results of this study there is a transient abnormality in thyroid function tests in patient undergoing elective major surgery and this abnormality due to surgical stress.