bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular Localization Patterns and Their Relationship to Photodynamic Activity of Pyropheophorbide‐a Derivatives
Authors: MacDonald Ian J. , Morgan Janet , Bellnier David A. , Paszkiewicz Geraldine ML , Whitaker James E. , Litchfield Debra J. , Dougherty Thomas J.
Published: January 2008

To determine if subcellular localization is important to photodynamic therapy (PDT) efficacy, an in vitro fluorescence microscopy study was conducted with a congeneric series of pyropheophorbide‐a derivatives in human pharyngeal squamous cell carcinoma (FaDu) cells and murine radiation‐induced fibrosarcoma (RIF) mutant cells. In the FaDu cells the octyl, decyl and dodecyl ether derivatives localized to the lysosomes at extracellular concentrations less than needed to produce a 50% cell kill (LD50). At extracellular concentrations equal or greater than the LD50 the compounds localized mainly to mitochondria. The propyl, pentyl, hexyl and heptyl ether derivatives localized mainly to the mitochondria at all concentrations studied. This suggested that mitochondria are a sensitive PDT target for these derivatives. Similar experiments were performed with two Photofrin®‐PDT resistant RIF cell lines, one of which was found to be resistant to hexyl ether derivative (C6) mediated‐PDT and the other sensitive to C6‐PDT relative to the parent line. At extracellular concentrations of C6 below the LD50 of each cell line, the mutants exhibited lysosomal localization. At concentrations above these values the patterns shifted to a mainly mitochondrial pattern. In these cell lines mitochondrial localization also correlated with PDT sensitivity. Localization to mitochondria or lysosomes appeared to be affected by the aggregation state of the congeners, all of which are highly aggregated in aqueous medium. Monomers apparently were the active fraction of these compounds because equalizing the extracellular monomer concentrations produced equivalent intracellular concentrations, photoxicity and localization patterns. Compounds that were mainly aggregates localized to the lysosomes where they were rendered less active. Mitochondria appear to be a sensitive target for pyro‐pheophorbide‐a‐mediated photodamage, and the degree of aggregation seems to be a determinant of the localization site.
HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus
Authors: Carper Michael J. , Cade W. Todd , Cam Margaret , Zhang Sheng , Shalev Anath , Yarasheski Kevin E. , Ramanadham Sasanka
Published: January 2008

Insulin resistance, hyperglycemia, and type 2 diabetes are among the sequelae of metabolic syndromes that occur in 60–80% of human immunodeficiency virus (HIV)-positive patients treated with HIV-protease inhibitors (PIs). Studies to elucidate the molecular mechanism(s) contributing to these changes, however, have mainly focused on acute, in vitro actions of PIs. Here, we examined the chronic (7 wk) in vivo effects of the PI indinavir (IDV) in male Zucker diabetic fatty ( fa/fa) (ZDF) rats. IDV exposure accelerated the diabetic state and dramatically exacerbated hyperglycemia and oral glucose intolerance in the ZDF rats, compared with vehicle-treated ZDF rats. Oligonucleotide gene array analyses revealed upregulation of suppressor of cytokine signaling-1 (SOCS-1) expression in insulin-sensitive tissues of IDV rats. SOCS-1 is a known inducer of insulin resistance and diabetes, and immunoblotting analyses revealed increases in SOCS-1 protein expression in adipose, skeletal muscle, and liver tissues of IDV-administered ZDF rats. This was associated with increases in the upstream regulator TNF-α and downstream effector sterol regulatory element-binding protein-1 and a decrease in IRS-2. IDV and other PIs currently in clinical use induced the SOCS-1 signaling cascade also in L6 myotubes and 3T3-L1 adipocytes exposed acutely to PIs under normal culturing conditions and in tissues from Zucker wild-type lean control rats administered PIs for 3 wk, suggesting an effect of these drugs even in the absence of background hyperglycemia/hyperlipidemia. Our findings therefore indicate that induction of the SOCS-1 signaling cascade by PIs could be an important contributing factor in the development of metabolic dysregulation associated with long-term exposures to HIV-PIs.
A Model of the Quorum Sensing System in Vibrio fischeri Using P Systems
Authors: Romero-Campero Francisco J. , Pérez-Jiménez Mario J.
Published: January 2008

Quorum sensing is a cell-density-dependent gene regulation system that allows an entire population of bacterial cells to communicate in order to regulate the expression of certain or specific genes in a coordinated way depending on the size of the population. We present a model of the quorum sensing system in Vibrio fischeri using a variant of membrane systems called P systems. In this framework each bacterium and the environment are represented by membranes, and the rules are applied according to an extension of Gillespie's algorithm called the multicompartmental Gillespie's algorithm. This algorithm runs on more than one compartment and takes into account the disturbance produced when chemical substances diffuse from one compartment or region to another one. Our approach allows us to examine the individual behavior of each bacterium as an agent as well as the emergent behavior of the colony as a whole and the processes of swarming and recruitment. Our simulations show that at low cell densities bacteria remain dark, while at high cell densities some bacteria start to produce light and a recruitment process takes place that makes the whole colony of bacteria do so. Our computational modeling of quorum sensing could provide insights leading to new applications where multiple agents need to robustly and efficiently coordinate their collective behavior based only on very limited information about the local environment.
Order-Dependent Coincidence Detection in Cerebellar Purkinje Neurons at the Inositol Trisphosphate Receptor
Authors: Sarkisov Dmitry V. , Wang Samuel S.-H.
Published: January 2008

Associative long-term depression (LTD) at cerebellar parallel fiber–Purkinje cell synapses is sensitive to the temporal order in which the parallel fiber is coactivated with the climbing fiber input, but how order sensitivity is achieved is unknown. Here we show that the cerebellar inositol-1,4,5-trisphosphate (IP3) receptor, whose activation is required for LTD induction, is sensitivein situto the order of presentation of its coagonists, IP3and cytoplasmic calcium. By focally photolyzing a novel caged IP3compound in dendritic spines, we find that pairing IP3with climbing fiber-mediated calcium entry leads to a large calcium release transient if the climbing fiber is activated up to 100 ms before or up to 500 ms after IP3uncaging. This asymmetric timing window for coactivation follows the kinetics of calcium removal and IP3unbinding from the receptor and is not limited by IP3metabolism. IP3receptor binding thus acts as an eligibility trace that can drive temporal order-dependent calcium release and LTD induction in Purkinje cells and event order-dependent sensory plasticity in the whole animal.
Lrig1 Is an Endogenous Inhibitor of Ret Receptor Tyrosine Kinase Activation, Downstream Signaling, and Biological Responses to GDNF
Authors: Ledda Fernanda , Bieraugel Oliver , Fard Shahrzad Shirazi , Vilar Marçal , Paratcha Gustavo
Published: January 2008

Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling has potent trophic effects on ventral midbrain dopaminergic, motor, sensory, and sympathetic neurons. The molecular mechanisms that restrict Ret receptor tyrosine kinase activation are not well understood. Here, we show that Lrig1, a transmembrane protein containing leucine-rich repeats and Ig-like domains in its extracellular region, acts in a negative feedback loop to regulate the activity of Ret receptor tyrosine kinase. In particular, we demonstrate that Lrig1 is capable of physically interacting with Ret and that Lrig1/Ret association inhibits GDNF binding, recruitment of Ret to lipid rafts, receptor autophosphorylation, and mitogen-activated protein kinase (MAPK) activation in response to GDNF. In neuronal cells, Lrig1 overexpression also inhibits GDNF/Ret-induced neurite outgrowth in a cell-autonomous manner. Downregulation of Lrig1 using small interference RNA knock-down experiments potentiates both neuronal differentiation and MAPK activation in response to GDNF. Together, these results provide an insight into Lrig1 function and establish a new physiological mechanism to restrict signaling and biological responses induced by GDNF and Ret in neuronal cells.
The Role of Hippocampal GluR1 and GluR2 Receptors in Manic-Like Behavior
Authors: Du Jing , Creson Thomas K. , Wu Long-Jun , Ren Ming , Gray Neil A. , Falke Cynthia , Wei Yanling , Wang Yun , Blumenthal Rayah , Machado-Vieira Rodrigo , Yuan Peixiong , Chen Guang , Zhuo Min , Manji Husseini K.
Published: January 2008

The cellular basis underlying the complex clinical symptomatology of bipolar disorder and the mechanisms underlying the actions of its effective treatments have not yet been fully elucidated. This study investigated the role of hippocampal synaptic AMPA receptors. We found that chronic administration of the antimanic agents lithium and valproate (VPA) reduced synaptic AMPA receptor GluR1/2 in hippocampal neuronsin vitroandin vivo. Electrophysiological studies confirmed that the AMPA/NMDA ratio was reduced in CA1 regions of hippocampal slices from lithium-treated animals. Reduction in GluR1 phosphorylation at its cAMP-dependent protein kinase A site by the synthetic peptide TAT-S845, which mimics the effects of lithium or VPA, was sufficient to attenuate surface and synaptic GluR1/2 levels in hippocampal neuronsin vitroandin vivo. Intrahippocampal infusion studies with the AMPA-specific inhibitor GYKI 52466 [4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)-benzenamine hydrochloride], a GluR1-specific TAT-S845 peptide, showed that GluR1/2 was essential for the development of manic/hedonic-like behaviors such as amphetamine-induced hyperactivity. These studies provide novel insights into the role of hippocampal GluR1/2 receptors in mediating facets of the manic syndrome and offer avenues for the development of novel therapeutics for these disorders.
Vasopressin Increases Locomotion through a V1a Receptor in Orexin/Hypocretin Neurons: Implications for Water Homeostasis
Authors: Tsunematsu Tomomi , Fu Li-Ying , Yamanaka Akihiro , Ichiki Kanako , Tanoue Akito , Sakurai Takeshi , van den Pol Anthony N.
Published: January 2008

Water homeostasis is a critical challenge to survival for land mammals. Mice display increased locomotor activity when dehydrated, a behavior that improves the likelihood of locating new sources of water and simultaneously places additional demands on compromised hydration levels. The neurophysiology underlying this well known behavior has not been previously elucidated. We report that the anti-diuretic hormone arginine-vasopressin (AVP) is involved in this response. AVP and oxytocin directly induced depolarization and an inward current in orexin/hypocretin neurons. AVP-induced activation of orexin neurons was inhibited by a V1a receptor (V1aR)-selective antagonist and was not observed in V1aR knock-out mice, suggesting an involvement of V1aR. Subsequently activation of phospholipase Cβ triggers an increase in intracellular calcium by both calcium influx through nonselective cation channels and calcium release from calcium stores in orexin neurons. Intracerebroventricular injection of AVP or water deprivation increased locomotor activity in wild-type mice, but not in transgenic mice lacking orexin neurons. V1aR knock-out mice were less active than wild-type mice. These results suggest that the activation of orexin neurons by AVP or oxytocin has an important role in the regulation of spontaneous locomotor activity in mice. This system appears to play a key role in water deprivation-induced hyperlocomotor activity, a response to dehydration that increases the chance of locating water in nature.
Retinoid Hyposignaling Contributes to Aging-Related Decline in Hippocampal Function in Short-Term/Working Memory Organization and Long-Term Declarative Memory Encoding in Mice
Authors: Mingaud Frédérique , Mormede Cécile , Etchamendy Nicole , Mons Nicole , Niedergang Betty , Wietrzych Marta , Pallet Véronique , Jaffard Robert , Krezel Wojciech , Higueret Paul , Marighetto Aline
Published: January 2008

An increasing body of evidence indicates that the vitamin A metabolite retinoic acid (RA) plays a role in adult brain plasticity by activating gene transcription through nuclear receptors. Our previous studies in mice have shown that a moderate downregulation of retinoid-mediated transcription contributed to aging-related deficits in hippocampal long-term potentiation and long-term declarative memory (LTDM). Here, knock-out, pharmacological, and nutritional approaches were used in a series of radial-arm maze experiments with mice to further assess the hypothesis that retinoid-mediated nuclear events are causally involved in preferential degradation of hippocampal function in aging. Molecular and behavioral findings confirmed our hypothesis. First, a lifelong vitamin A supplementation, like short-term RA administration, was shown to counteract the aging-related hippocampal (but not striatal) hypoexpression of a plasticity-related retinoid target-gene, GAP43 (reverse transcription-PCR analyses, experiment 1), as well as short-term/working memory (STWM) deterioration seen particularly in organization demanding trials (STWM task, experiment 2). Second, using a two-stage paradigm of LTDM, we demonstrated that the vitamin A supplementation normalized memory encoding-induced recruitment of (hippocampo-prefrontal) declarative memory circuits, without affecting (striatal) procedural memory system activity in aged mice (Fos neuroimaging, experiment 3A) and alleviated their LTDM impairment (experiment 3B). Finally, we showed that (knock-out, experiment 4) RA receptor β and retinoid X receptor γ, known to be involved in STWM (Wietrzych et al., 2005), are also required for LTDM. Hence, aging-related retinoid signaling hypoexpression disrupts hippocampal cellular properties critically required for STWM organization and LTDM formation, and nutritional vitamin A supplementation represents a preventive strategy. These findings are discussed within current neurobiological perspectives questioning the historical consensus on STWM and LTDM system partition.
Pigment Dispersing Factor-Dependent and -Independent Circadian Locomotor Behavioral Rhythms
Authors: Sheeba Vasu , Sharma Vijay K. , Gu Huaiyu , Chou Yu-Ting , O'Dowd Diane K. , Holmes Todd C.
Published: January 2008

Circadian pacemaker circuits consist of ensembles of neurons, each expressing molecular oscillations, but how circuit-wide coordination of multiple oscillators regulates rhythmic physiological and behavioral outputs remains an open question. To investigate the relationship between the pattern of oscillator phase throughout the circadian pacemaker circuit and locomotor activity rhythms inDrosophila, we perturbed the electrical activity and pigment dispersing factor (PDF) levels of the lateral ventral neurons (LNv) and assayed their combinatorial effect on molecular oscillations in different parts of the circuit and on locomotor activity behavior. Altered electrical activity of PDF-expressing LNv causes initial behavioral arrhythmicity followed by gradual long-term emergence of two concurrent short- and long-period circadian behavioral activity bouts in ∼60% of flies. Initial desynchrony of circuit-wide molecular oscillations is followed by the emergence of a novel pattern of period (PER) synchrony whereby two subgroups of dorsal neurons (DN1 and DN2) exhibit PER oscillation peaks coinciding with two activity bouts, whereas other neuronal subgroups exhibit a single PER peak coinciding with one of the two activity bouts. The emergence of this novel pattern of circuit-wide oscillator synchrony is not accompanied by concurrent change in the electrical activity of the LNv. In PDF-null flies, altered electrical activity of LNv drives a short-period circadian activity bout only, indicating that PDF-independent factors underlie the short-period circadian activity component and that the long-period circadian component is PDF-dependent. Thus, polyrhythmic behavioral patterns in electrically manipulated flies are regulated by circuit-wide coordination of molecular oscillations and electrical activity of LNv via PDF-dependent and -independent factors.
Alzheimer's Disease (AD)-Like Pathology in Aged Monkeys after Infantile Exposure to Environmental Metal Lead (Pb): Evidence for a Developmental Origin and Environmental Link for AD
Authors: Wu Jinfang , Basha Md. Riyaz , Brock Brian , Cox David P. , Cardozo-Pelaez Fernando , McPherson Christopher A. , Harry Jean , Rice Deborah C. , Maloney Bryan , Chen Demao , Lahiri Debomoy K. , Zawia Nasser H.
Published: January 2008

The sporadic nature of Alzheimer's disease (AD) argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead (Pb) during brain development predetermined the expression and regulation of the amyloid precursor protein (APP) and its amyloidogenic β-amyloid (Aβ) product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 (β-site APP cleaving enzyme 1)] as well as their transcriptional regulator (Sp1) were elevated in aged (23-year-old) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Aβ staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD.
The Magnocellular Mediodorsal Thalamus is Necessary for Memory Acquisition, But Not Retrieval
Authors: Mitchell Anna S. , Gaffan David
Published: January 2008

Damage to the magnocellular mediodorsal thalamic nucleus (MDmc) in the human brain is associated with both retrograde and anterograde amnesia. In the present study we made selective neurotoxic MDmc lesions in rhesus monkeys and compared the effects of these lesions on memory acquisition and retrieval. Monkeys learned 300 unique scene discriminations preoperatively and retention was assessed in a one-trial preoperative retrieval test. Bilateral neurotoxic lesions of the MDmc, produced by 10 × 1 μl injections of a mixture of ibotenate and NMDA did not affect performance in the postoperative one-trial retrieval test. In contrast, new postoperative learning of a further 100 novel scene discriminations was substantially impaired. Thus, MDmc is required for new learning of scene discriminations but not for their retention and retrieval. This finding is the first evidence that MDmc plays a specific role in memory acquisition.
AGE-RELATED SERIAL PLASMA CITRULLINE LEVELS IN PRETERM NEONATES
Authors: Ioannou Hariklia , Avgoustides-Savvopoulou Persephone , Diamanti Elisavet , Tsampoura Zoi , Drosou-Agakidou Vasiliki
Published: January 2008

INTRODUCTION: Citrulline is a nonessential amino acid that is synthesized almost exclusively in the small intestine. In adults and children with short-bowel syndrome, citrulline has served as a reliable index of the remaining small intestine length. Citrulline is also a precursor of arginine, the role of which is crucial for neonatal metabolism and growth.

OBJECTIVE: We sought to determine serial plasma citrulline levels of preterm neonates to assess levels in accordance with age and intestinal maturation, which may serve as a baseline in the event of intestinal abnormalities such as necrotizing enterocolitis (a devastating complication in this age group).

METHODS: We measured serial plasma citrulline levels in 18 clinically stable neonates (gestational age: ≤32 weeks; birth weight: 1000–1750 g) on days 2, 7, 14, 21, and 28. Quantitative analysis of plasma citrulline levels was performed by ion-exchange chromatography with postcolumn derivatization.

RESULTS: In the study population, mean plasma citrulline levels showed a statistically significant increase from 19 ± 4 μmol/L on day 2 and 20 ± 4 μmol/L on day 7 to 23 ± 4 μmol/L on day 14, 29 ± 5 μmol/L on day 21, and 31 ± 5 μmol/L on day 28 (P < .01). The route of feeding did not seem to have an affect on plasma levels of citrulline (similar values were obtained from neonates who were fed enterally and parenterally on day 7).

CONCLUSIONS: Citrulline levels in normal preterm neonates seem to be age-related and may serve as reference values, which facilitates the evaluation of compromised intestinal function in preterm neonates with severe gastrointestinal problems.
TOPICAL COCONUT OIL APPLICATION REDUCES TRANSEPIDERMAL WATER LOSS IN PRETERM VERY LOW BIRTH WEIGHT NEONATES: A RANDOMIZED CLINICAL TRIAL
Authors: Nangia Sushma , Paul Vinod , Chawla Deepak , Deorari Ashok
Published: January 2008

INTRODUCTION: Topical emollients have been shown to reduce transepidermal water loss (TEWL). Such an effect of coconut oil (often used in traditional massage of infants in India) has not been studied.

OBJECTIVE: Our goal was to determine the efficacy of topical coconut-oil application in reducing TEWL in preterm very low birth weight (VLBW) neonates.

METHODS: Seventy-four preterm VLBW infants were randomly assigned at 12 hours of age to either 4 mL of topical coconut-oil application every 12 hours for 7 days (n = 37) or no oil application (n = 37). TEWL was measured at 12 hours of age and thereafter every 12 hours for 7 days in both groups by using a Vapometer (Delfin Technologies, Kuopio, Finland), a portable closed-chamber evaporimeter. The ambient and skin-surface relative humidity and temperature were recorded simultaneously.

RESULTS: Birth weight (1213 ± 214 vs 1164 ± 208 g), gestation (32 ± 2 vs 31 ± 2 weeks), and other baseline variables were comparable between the 2 groups. TEWL was significantly lower in the infants in the coconut-oil group at each point of measurement. Although TEWL declined for those in both groups during the first week of life, proportional reduction in TEWL in the infants in the coconut-oil group was much greater compared with controls. Significantly lower TEWL in the infants in the coconut-oil group persisted after adjusting for differences in baseline variables by using a generalized estimating equation population-averaged model (an advanced form of regression analysis) (mean difference: 6.8 g/m2 per hour all during first week of life [95% confidence interval: 3.5–10.2]; P = .000).

CONCLUSIONS: Coconut-oil application in preterm VLBW neonates reduced TEWL by as much as 46%. Such an impact is expected to be of clinical importance, because it could reduce initial weight loss, promote better growth, and reduce fluid requirements.
LONG-TERM FOLLOW-UP RESULTS OF PERCUTANEOUS CATHETER INTERVENTION FOR CORONARY ARTERY LESIONS AFTER KAWASAKI DISEASE: MULTICENTER COLLABORATIVE STUDY
Authors: Ishii Masahiro , Muta Hiromi , Nakahata Yayoi , Ogata Syouhei , Kimura Sumito , Ayusawa Mamoru , Iemura Motofumi , Ogawa Syunichi
Published: January 2008

INTRODUCTION: The long-term prognosis in patients with Kawasaki disease (KD) after percutaneous coronary intervention (PCI) remains unclear.

OBJECTIVE: We sought to clarify the long-term results of PCI for KD.

METHODS: Patients who developed coronary stenotic lesions caused by KD and were treated with PCI were investigated. Restenosis or obstruction was diagnosed when the stenosis was ≥75% according to coronary angiography or ischemic change was observed by myocardial perfusion imaging.

RESULTS: A total of 55 stenotic lesions were reported in 49 patients in 5 institutions. The types of PCI included percutaneous transluminal coronary angioplasty (n = 22), stent implantation (n = 7), percutaneous transluminal coronary rotational ablation (PTCRA) (n = 22), and combination of PTCRA with stent implantation (n = 4). Median age at PCI was 14.5 years, and the median follow-up period in the PCI group was 6.3 years. of 55 stenotic lesions in the PCI group, 52 (95%) were dilated successfully by PCI. Immediate complications in the PCI group included neoaneurysm in 5 patients, transient bradycardia in 3 patients, and atrial fibrillation in 1 patient. Treatment for restenosis in the PCI group included re-PCI in 3 patients, coronary artery bypass grafting in 6 patients, and heart transplantation in 1 patient. No patient in the PCI group died. There was no difference in effectiveness among the 3 PCI devices (percutaneous transluminal coronary angioplasty versus stent implantation versus PTCRA: log-rank test, P = .3).

CONCLUSIONS: PCI for KD can be accomplished and can be effective in the long-term.
ELECTRON MICROSCOPIC ANALYSIS OF BACTERIAL BIOFILM ON TRACHEAL TUBES REMOVED FROM INTUBATED NEONATES AND THE RELATIONSHIP BETWEEN BACTERIAL BIOFILM AND LOWER RESPIRATORY INFECTIONS
Authors: Jialin Yu , Boman Chen , Guanxin Liu , Linyan Hu , Luquan Li
Published: January 2008

INTRODUCTION: Recurrent neonatal lower respiratory infections caused by endotracheal tubes (ETTs) may be related to the bacterial biofilm on them.

OBJECTIVE: We aimed to investigate the microbial biofilm on the surface of ETTs removed from neonates with intubated ventilation to explore the relationship between ETT biofilm and the lower respiratory infections.

METHODS: Twenty ETTs used in intubated neonates were examined for the presence of biofilm on their surface by scanning electron microscopy, and bacteria harvested from the surface of ETTs and the secretions of lower respiratory tracts were isolated, identified, and assessed for antimicrobial susceptibility.

RESULTS: Scanning electron microscopy showed that the incidence of microbial colonization was 60% (12 of 20) when the use of tubes exceeded 2 days, biofilm formation was observed ∼3 days after intubation, and its architecture became more mature and complex when the duration exceeded 3 days. There were 14 positive cultures from ETTs (70%, including 4 normal flora), in which 7 kinds of pathogens were isolated; in 13 cultures from the secretions of lower respiratory tract (65%, including 1 normal flora), 10 kinds of pathogens were isolated. Seven samples had the same pathogen both on the surface of ETTs and in the secretions of the lower respiratory tract, which accounted for 50 of the positive cultures from ETTs. The Gram-negative bacteria isolated from the surface of ETTs and the secretions of lower respiratory tract presented multiresistance to antibiotics.

CONCLUSIONS: The ETT biofilm develops into a mature and complex form on the basis of the duration of tube use. There is a possible positive correlation between them. There is correlation between microbial biofilm formation on the surface of ETTs and lower respiratory tract infection in intubated neonates who are ventilated for a prolonged period of time. ETT biofilm could be a likely source of recurrent infection.
SOCIAL FACTORS ASSOCIATED WITH CHILD ABUSE AND NEGLECT IN GUADALAJARA, MEXICO
Authors: Vega-Lopez Maria Guadalupe , Gonzalez-Perez Guillermo J. , Ana Valle MPH , Flores Maria E , Romero-Valle Samuel , Quintero Ing Pedro P.
Published: January 2008

INTRODUCTION: Cases of child abuse and neglect have increased in Mexico, but few studies have been carried out to examine the factors associated with this health problem.

OBJECTIVE: With this study we sought to identify social factors associated with child abuse and neglect and to construct a predictor model of child maltreatment in children younger than 7 years in Guadalajara, Mexico.

METHODS: A case-control study was designed; cases were selected randomly from the register of maltreated children younger than 7 years by the DIF (the public institution that provides assistance to families in Mexico) during 2002 (N = 205). Controls were chosen randomly from the register of children assisted in other DIF programs in 2002 (N = 379). A multivariate logistic regression model was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs).

RESULTS: In the multivariate analysis, 6 factors were statistically associated with child maltreatment: maternal drug addiction (OR: 15.3 [95% CI: 1.8–127.6]), mother without steady partner (OR: 3.0 [95% CI: 1.9–4.6]), bad family relationships (OR: 1.3 [95% CI: 1.1–4.2]), the child has “tantrums” (OR: 1.8 [95% CI: 1.2–2.8]), the child's behavior irritates the parents (OR: 1.5 [95% CI: 1.1–2.1]), and overcrowding (OR: 1.5 [95% CI: 1.1–2.2]).

CONCLUSIONS: According to the constructed model, if a child were simultaneously exposed to all these risk factors, he or she would have a very high probability of being a maltreated child. The findings show that public health institutions can play an important role in designing timely intervention strategies directed at avoiding or reducing the cases of child abuse and neglect.
CLINICAL MARKERS THAT ENHANCE ETIOLOGIC YIELD IN GLOBAL DEVELOPMENTAL DELAY
Authors: Chung B. H. Y. , Wong V.
Published: January 2008

INTRODUCTION: Etiology remains unknown in 30% to 50% cases of children with global developmental delay (GDD). A selective approach has been recommended to increase etiologic yield.

OBJECTIVE: Our aim was to identify clinical markers that enhance diagnostic yield of GDD at initial assessment.

METHODS: The charts of all patients with GDD (N = 577) followed up at the Duchess of Kent Child Assessment Centre were reviewed. GDD was defined as significant delay (<2 SD) in ≥2 developmental domains. Nine clinical items at initial assessment (gender, severity of delay, parental consanguinity, family history, behavioral disturbance, head size, facial dysmorphism, malformations, and neurologic deficits) were correlated with the likelihood of finding an etiology for GDD.

RESULTS: A significant threshold effect was found between mild and moderate GDD (positive likelihood ratio (LR+]: 1.9; negative likelihood ratio [LR−]: 0.72). Other items that significantly affected diagnostic yield were (1) female gender (LR+: 1.62; LR−: 0.79), (2) behavioral trait (LR+: 0.24; LR−: 1.67), (3) microcephaly (LR+: 2.78; LR−: 0.79), (4) presence of facial dysmorphism (LR+: 2.65; LR−: 0.65), (5) malformation (LR+: 1.49; LR−: 0.50), and (6) neurologic deficits (LR+: 2.86; LR−: 0.32). A dose-response relationship was found between LR+ and the number of facial dysmorphisms and malformations.

CONCLUSIONS: Most checklists used for GDD are syndrome specific (eg, fragile X syndrome checklists). These 7 clinical markers are useful in the initial assessment, even if no specific diagnosis is suspected. Unique statistical characteristics of LRs allow for a wide application in different clinical settings.
Visual outcome after surgery in patients with suprasellar tumors and preoperative blindness
Authors: Suri Ashish , Narang Karanjit Singh , Sharma Bhawani Shankar , Mahapatra Ashok Kumar
Published: January 2008

Object

The purpose of this paper was to study the visual outcome after surgery in patients with suprasellar tumors who experienced preoperative blindness in 1 or both eyes.

Methods

All patients with suprasellar tumors and no perception of light in 1 or both eyes and who underwent surgery between May 2002 and May 2006 were included in this retrospective study. Outcome was analyzed at discharge from the hospital and at follow-up. There were a total of 79 patients (51 males and 28 females, age range 5–70 years). There were 37 cases of pituitary adenomas, 19 craniopharyngiomas, 18 meningiomas, and 5 other tumors. Preoperatively 61 patients had uniocular blindness and 18 patients had binocular blindness. Of all 158 eyes, 97 (61.4%) were blind at admission and these eyes were analyzed. Sixty-three patients (79.7%) presented with headache and 14 (17.7%) with hypothalamic symptoms. Nearly one fourth (24%) of patients with a pituitary adenoma had a history of apoplexy. The duration of visual decline ranged from 3 days to 7 years, and the duration of blindness ranged from 1 day to 3 years. Patients underwent either transcranial or transsphenoidal tumor decompression.

Results

At discharge from the hospital visual improvement was exhibited in 23 (29%) of 79 patients and 27 (27.8%) of 97 eyes. Improvement to serviceable vision occurred in 7 (8.9%) of 79 patients and in 8 (8.2%) of 97 eyes with pre-operative blindness. After surgery, visual improvement was noted in 15 (24.6%) of 61 patients with uniocular blindness and 8 (44.4%) of 18 patients with binocular blindness. However, serviceable vision was restored in 5 (8.2%) of 61 patients with uniocular and 2 (11.1%) of 18 patients with binocular blindness. Bivariate analysis revealed male sex, shorter duration of blindness, presence of apoplexy, sellar tumor extension, soft tumor consistency, operative evidence of hemorrhage in tumor, and tumor histopathology (pituitary adenoma) to have significant impact on the outcome. Multivariate analysis revealed duration of blindness for > 12 weeks, apoplexy, and sellar extension to have a significant impact on visual outcome.

Conclusions

The present study is the largest in the existing medical literature to evaluate the factors affecting visual outcome after surgery of suprasellar tumors with preoperative blindness.
Extended transsphenoidal approach for surgical management of pituitary adenomas invading the cavernous sinus
Authors: Kitano Masahiko , Taneda Mamoru , Shimono Taro , Nakao Yuzo
Published: January 2008

Object

The authors devised an extended transsphenoidal approach involving a submucosal posterior ethmoidectomy that allows for adequate exposure of the cavernous sinus. To evaluate the adequacy of this approach for removal of adenomas invading the cavernous sinus, the authors retrospectively analyzed the surgical outcomes obtained in treated patients.

Methods

During a 9-year period, 36 patients with pituitary adenomas extending into the cavernous sinus underwent tumor removal at Kinki University Hospital. In the authors' technique of extended transsphenoidal surgery, the inferior wall of the affected cavernous sinus was entirely exposed, not only to permit safe removal of the tumor but also to secure the petrous portion of the internal carotid artery (ICA). For prevention of intraoperative injury to the cranial nerves, a low-profile pressure sensor was attached on the eyelid to detect eye movements in response to electrical stimulation of the cranial nerves.

Results

Total or subtotal tumor removal was achieved in 72% of 36 patients. In eight (67%) of 12 patients with growth hormone–secreting adenomas, hormonal remission was achieved postoperatively. Postoperative transient double vision was observed in 27% of the patients, but no serious complications, such as permanent cranial nerve palsy or ICA injury, occurred.

Conclusions

These reasonable surgical results obtained in the present series of patients suggest that the extended transsphenoidal approach is safe and effective for removal of adenomas within the cavernous sinus. These preliminary results may lead to a reevaluation of the role of surgery as the therapeutic strategy for invasive pituitary adenomas.
Trigeminal trophic syndrome of all three nerve branches: an underrecognized complication after brain surgery
Authors: Lukšić Ivica , Lukšić Ivana , Šestan-Crnek Sandra , Virag Mihajlo , Macan Darko
Published: January 2008

✓The authors report a case of trigeminal trophic syndrome (TTS) that occurred as a complication of a neurosurgical procedure. Three years after a second surgical treatment for a meningioma of the cerebellopontine angle, this 32-year-old woman developed TTS with progressive skin ulcers on the left ala nasi and the left side of the forehead and chin. Trigeminal trophic syndrome is an extremely rare cause of facial ulceration. It occurs as a consequence of trigeminal nerve damage or impaired central sensory connections. To the authors' knowledge, this is the first report of lesions in the dermatomes of all three branches of the nerve after a neurosurgical procedure. Early recognition of this disorder is important, as treatment is difficult and often unsatisfactory. Many clinicians are not aware of this disease, thus, it may be more common than previously thought. The importance of recognizing and diagnosing TTS, as well as its treatment, are discussed.
A proposed grading system for arteriovenous malformations
Authors: Spetzler Robert F. , Martin Neil A.
Published: January 2008

✓ An important factor in making a recommendation for treatment of a patient with arteriovenous malformation (AVM) is to estimate the risk of surgery for that patient. A simple, broadly applicable grading system that is designed to predict the risk of morbidity and mortality attending the operative treatment of specific AVM's is proposed. The lesion is graded on the basis of size, pattern of venous drainage, and neurological eloquence of adjacent brain. All AVM's fall into one of six grades. Grade I malformations are small, superficial, and located in non-eloquent cortex; Grade V lesions are large, deep, and situated in neurologically critical areas; and Grade VI lesions are essentially inoperable AVM's.

Retrospective application of this grading scheme to a series of surgically excised AVM's has demonstrated its correlation with the incidence of postoperative neurological complications. The application of a standardized grading scheme will enable a comparison of results between various clinical series and between different treatment techniques, and will assist in the process of management decision-making.
Transventricular, transaqueductal scope-in-scope endoscopic excision of fourth ventricular neurocysticercosis: a series of 13 cases and a review
Authors: Suri Ashish , Goel Rohit Kumar , Ahmad Faiz Uddin , Vellimana Ananth Kesav , Sharma Bhawani Shankar , Mahapatra Ashok Kumar
Published: January 2008

Object

Neurocysticercosis (NCC) is the most common parasitic infestation of the central nervous system worldwide. In patients presenting with acute hydrocephalus due to intraventricular NCC, surgery is the only option. Still, there is no consensus regarding the optimal surgical strategy, although neuroendoscopic excision is a promising method. However, the literature regarding the use of this modality in fourth ventricular NCC is scarce. The authors describe a series of patients with fourth ventricular NCC treated endoscopically.

Methods

The clinical records of 13 patients with fourth ventricular NCC who had presented with hydrocephalus were retrospectively analyzed. A fourth ventricular cyst was completely excised in all patients by using a transventricular, transaqueductal “scope-in-scope” endoscopic technique. Twelve endoscopic third ventriculostomies and 1 septostomy had been performed.

Results

Shunt placement was avoided in all patients. There were minimal peri- and postoperative complications. The mean duration of follow-up was 22.3 months (range 3–41 months). All patients had an improved clinical outcome. Follow-up neuroimaging revealed no residual lesion and a decreased ventricle size in all patients.

Conclusions

The present series of patients with fourth ventricular NCC is the largest in the existing English-language medical literature. Endoscopic fourth ventricular cysticercal cyst excision along with internal cerebrospinal fluid diversion via endoscopic third ventriculostomy is an effective alternative to open microneurosurgical procedures and avoids shunt placement and its related complications.
Multiple ruptured cerebral aneurysms in a child with Takayasu arteritis
Authors: Magge Suresh N. , Chen H. Isaac , Stiefel Michael F. , Ernst Linda , Cahill Ann Marie , Hurst Robert , Storm Phillip B.
Published: January 2008

✓The authors report the case of an 18-month-old girl who presented with a ruptured anterior communicating artery aneurysm, and who was later diagnosed with Takayasu arteritis. Her initial aneurysm was successfully treated with clip application. However, over a 6-month period she had multiple ruptures from new and rapidly recurring aneurysms adjacent to the clips. These aneurysms were treated with repeated craniotomy and clip application and then with endovascular coil placement. Aneurysmal subarachnoid hemorrhage is a rare presentation of Takayasu arteritis. To the authors' knowledge, this is the youngest reported patient with Takayasu arteritis to present with a ruptured cerebral aneurysm.
Lumbar puncture and surgical intervention in a child with undiagnosed fibrodysplasia ossificans progressiva
Authors: Zaghloul Kareem A. , Heuer Gregory G. , Guttenberg Marta D. , Shore Eileen M. , Kaplan Frederick S. , Storm Phillip B.
Published: January 2008

✓ Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by congenital malformation of the great toes and episodes of soft tissue swelling that lead to progressive heterotopic ossification. The genetic cause of FOP was recently discovered to be a recurrent missense activating mutation in the activin A type I receptor, a bone morphogenetic protein type I receptor in all classically affected individuals worldwide. The authors present a child with the classic features of previously undiagnosed FOP who developed a paraspinal soft-tissue mass after a lumbar puncture for a fever workup. Excision of the mass resulted in a massive inflammatory response leading to progression of heterotopic ossification. Awareness of the classic clinical features of FOP prior to the appearance of heterotopic ossification can prompt early clinical diagnosis and confirmation through genetic testing, thus avoiding interventions that lead to irreversible iatrogenic harm.
Anterior cervical discectomy and interbody fusion by endoscopic approach: a preliminary report
Authors: Tan Jiangwei , Zheng Yanping , Gong Liangtai , Liu Xinyu , Li Jianmin , Du Wei
Published: January 2008

Object

The authors report the short-term results of anterior cervical discectomy and interbody fusion performed via an endoscopic approach.

Methods

Thirty-six patients who underwent anterior cervical discectomy and fusion (ACDF) performed using endoscopic surgery were selected for this study. The indications for surgery were cervical disc herniation caused by neck injury, spondylotic myelopathy, cervical radiculopathy, and solitary ossification of the posterior longitudinal ligament (OPLL). The involved levels included C3–4, C4–5, C5–6, and C6–7. The working channel was inserted through a 20-mm transverse incision, the protruding discs or area of OPLL were excised for complete decompression, and then an appropriate intervertebral polyetheretherketone fusion cage was implanted.

Results

The time spent in surgery was 120 minutes on average (range 50–150 minutes), and the mean blood loss was 55 ml (range 20–140 ml). There were no intraoperative complications and no symptoms of irritation in the laryngopharynx after surgery. However, postoperative hemorrhage of the incision occurred in 1 case. The follow-up period ranged from 26–50 months (mean 38.5 months). Postoperative Japanese Orthopaedic Association and visual analog scale scores improved significantly.

Conclusions

Endoscopic surgery for ACDF can produce satisfactory results in patients with cervical disc herniation, cervical myelopathy, or radiculopathy. The optimal levels for this procedure are C4–5 and C5–6. Compared with a traditional approach, this technique has great advantages in terms of cosmetic results, intraoperative visualization, and postoperative recovery course. Nevertheless, every precaution should be taken to avoid possible complications, such as postoperative hemorrhage.
Acute and delayed implantation of positively charged 2-hydroxyethyl methacrylate scaffolds in spinal cord injury in the rat
Authors: Hejcl Ales , Urdzikova Lucie , Sedy Jiri , Lesny Petr , Pradny Martin , Michalek Jiri , Burian Martin , Hajek Milan , Zamecnik Josef , Jendelova Pavla , Sykova Eva
Published: January 2008

Object

Hydrogels are nontoxic, chemically inert synthetic polymers with a high water content and large surface area that provide mechanical support for cells and axons when implanted into spinal cord tissue.

Methods

Macroporous hydrogels based on 2-hydroxyethyl methacrylate (HEMA) were prepared by radical copolymerization of monomers in the presence of fractionated NaCl particles. Male Wistar rats underwent complete spinal cord transection at the T-9 level. To bridge the lesion, positively charged HEMA hydrogels were implanted either immediately or 1 week after spinal cord transection; control animals were left untreated. Histological evaluation was performed 3 months after spinal cord transection to measure the volume of the pseudocyst cavities and the ingrowth of tissue elements into the hydrogels.

Results

The hydrogel implants adhered well to the spinal cord tissue. Histological evaluation showed ingrowth of connective tissue elements, blood vessels, neurofilaments, and Schwann cells into the hydrogels. Morphometric analysis of lesions showed a statistically significant reduction in pseudocyst volume in the treated animals compared with controls and in the delayed treatment group compared with the immediate treatment group (p < 0.001 and p < 0.05, respectively).

Conclusions

Positively charged HEMA hydrogels can bridge a posttraumatic spinal cord cavity and provide a scaffold for the ingrowth of regenerating axons. The results indicate that delayed implantation can be more effective than immediate reconstructive surgery.
Production of Papillomavirus‐Based Gene Transfer Vectors
Authors: Buck Christopher B. , Thompson Cynthia D.
Published: January 2008

Papillomaviruses are a diverse group of pathogens that infect the skin and mucosal tissues of humans and various animal species. The viral genome is a circular, double‐stranded DNA molecule ∼8‐kb in length. The non‐enveloped papillomavirus capsid is composed of a virally encoded major coat protein, L1, and a minor coat protein, L2. L1 and L2 co‐assemble when expressed in mammalian cells, and can promiscuously encapsidate essentially any <8‐kb plasmid present in the cell nucleus. In the last several years, there has been rapid development of techniques for intracellular production of papillomavirus‐based gene transfer vectors (also known as pseudoviruses). This unit outlines the production and propagative amplification of papillomaviral vectors. The system represents a highly tractable method for converting pre‐existing mammalian expression plasmids into infectious virus stocks. The resulting vectors have utility for in vitro, as well as in vivo gene delivery applications. Curr. Protoc. Cell Biol. 37:26.1.1‐26.1.19. © 2007 by John Wiley & Sons, Inc.
Using the MetaCyc Pathway Database and the BioCyc Database Collection
Authors: Caspi Ron , Karp Peter D.
Published: January 2008

The MetaCyc database (http://metacyc.org) is a collection of more than a thousand metabolic pathways from a wide variety of organisms, collected from the literature by manual curation. BioCyc contains more than 370 Pathway/Genome Databases, each of which describes the genome and predicted metabolic pathways of a single organism, as computationally predicted from the annotated genomes, using MetaCyc data as a reference. The protocols in this unit introduce the user to the extensive data content available in MetaCyc and BioCyc, and to mechanisms for querying, visualizing, and analyzing these data using the Pathway Tools software. Curr. Protoc. Bioinform. 20:1.17.1‐1.17.51. © 2007 by John Wiley & Sons, Inc.