Posterior segment Intra-Ocular Implant (IOL) dislocation: Predisposing factors, surgical management, outcome analysis.

PURPOSE: To evaluate the predisposing factors, management and visual prognosis of intraocular Lens (IOL) dislocation into the posterior segment. METHODS: The cases of posterior IOL dislocation from January 2012 to May 2017 at 2 centers were reviewed. Only eyes with dislocations requiring IOL explantation or repositioning were included. Predisposing factors, interval between cataract surgery and IOL dislocation, circumstances of onset, management, and postoperative complications are reported. RESULTS: 72 eyes of 72 patients were included. The mean age was 67.6 years. 47 patients (68%) were men. The mean time interval from cataract surgery to IOL dislocation was significantly shorter in the out-of-the bag group than the in-the-bag IOL dislocation group (3.8 months vs 132 months, P=0.002). Predisposing factors for out-of-the-bag IOL dislocation were mainly capsular rupture and/or zonular dehiscence (83%) after complicated cataract surgery. The predisposing factors for in-the-bag IOL dislocation were high myopia (40%), pseudoexfoliation syndrome (40%), previous vitrectomy (38%), or Marfan syndrome (3%) with uneventful cataract surgery. The type of luxated implant was mainly a 3-piece foldable IOL (50%), followed by foldable one-piece IOL (28%) and a rigid one-piece IOL (17%). Most cases of posterior chamber IOL dislocation occurred spontaneously (80%) without a trigger event. Management consisted of a posterior approach in 24 cases (33%) or an anterior approach in 48 cases (67%), associated with IOL repositioning in 20 eyes (28%), and IOL replacement in 34 eyes (47%). Finally, 18 eyes (25%) were left aphakic. Postoperative complications occurred in 7 cases (9.7%). CONCLUSIONS: Predisposing factors and time from cataract surgery to IOL dislocation were different for out-of-the bag versus in-the-bag IOL dislocation. Management of IOL dislocation varied considerably, depending on surgeon preference and experience. Surgery for IOL dislocation significantly improved best corrected visual acuity and was associated with a low complication rate.

Trade-Offs of Escherichia coli Adaptation to an Intracellular Lifestyle in Macrophages.

The bacterium Escherichia coli exhibits remarkable genomic and phenotypic variation, with some pathogenic strains having evolved to survive and even replicate in the harsh intra-macrophage environment. The rate and effects of mutations that can cause pathoadaptation are key determinants of the pace at which E. coli can colonize such niches and become pathogenic. We used experimental evolution to determine the speed and evolutionary paths undertaken by a commensal strain of E. coli when adapting to intracellular life. We estimated the acquisition of pathoadaptive mutations at a rate of 10-6 per genome per generation, resulting in the fixation of more virulent strains in less than a hundred generations. Whole genome sequencing of independently evolved clones showed that the main targets of intracellular adaptation involved loss of function mutations in genes implicated in the assembly of the lipopolysaccharide core, iron metabolism and di- and tri-peptide transport, namely rfaI, fhuA and tppB, respectively. We found a substantial amount of antagonistic pleiotropy in evolved populations, as well as metabolic trade-offs, commonly found in intracellular bacteria with reduced genome sizes. Overall, the low levels of clonal interference detected indicate that the first steps of the transition of a commensal E. coli into intracellular pathogens are dominated by a few pathoadaptive mutations with very strong effects.

Analyses of herpes simplex virus type 1 latency and reactivation at the single cell level using fluorescent reporter mice.

Herpes simplex virus type 1 (HSV-1) establishes a latent infection in sensory neurons from which the virus can periodically reactivate. Whilst latency establishment is thought to result from a failure to express immediate-early genes, we have previously shown that subpopulations of the latent neuronal reservoir have undergone lytic promoter activation prior to latency establishment. In the present study, we have investigated the biological properties of such latently infected neuronal subpopulations using Ai6 fluorescent reporter mice. Using this system we have determined that prior ICP0 or TK promoter activation does not correlate with increased latent virus DNA loads within individual cells and that neurons with evidence of historical lytic cycle promoter activity exhibit a comparable frequency of reactivation to that of the general latent cell population. Comparison of viral DNA content within cells harbouring latent HSV-1 genomes and those undergoing the earliest stages of reactivation has revealed that reactivation can initiate from cells harbouring a wide range of HSV-1 genome copies, but that exiting latency is biased towards cells bearing higher latent virus DNA loads.

Influence of herpes simplex virus 1 latency-associated transcripts on the establishment and maintenance of latency in the ROSA26R reporter mouse model.

Herpes simplex virus 1 (HSV-1) can establish life-long latent infection in sensory neurons, from which periodic reactivation can occur. During latency, viral gene expression is largely restricted to the latency-associated transcripts (LATs). While not essential for any phase of latency, to date the LATs have been shown to increase the efficiency of both establishment and reactivation of latency in small-animal models. We sought to investigate the role of LAT expression in the frequency of latency establishment within the ROSA26R reporter mouse model utilizing Cre recombinase-encoding recombinant viruses harboring deletions of the core LAT promoter (LAP) region. HSV-1 LAT expression was observed to influence the number of latently infected neurons in trigeminal but not dorsal root ganglia. Furthermore, the relative frequencies of latency establishment of LAT-positive and LAT-negative viruses are influenced by the inoculum dose following infection of the mouse whisker pads. Finally, analysis of the infected cell population at two latent time points revealed a relative loss of latently infected cells in the absence of LAT expression. We conclude that the HSV-1 LATs facilitate the long-term stability of the latent cell population within the infected host and that interpretation of LAT establishment phenotypes is influenced by infection methodology.

Increases in dentin-bond strength if doubling application time of an acetone-containing one-step adhesive.

This study investigated the microtensile bond strength (microTBS) of a one-step self-etching adhesive to human dentin and bovine enamel following different bonding treatments. Occlusal portions of human molars and labial surfaces of bovine incisors were ground flat to provide uniform dentin and enamel surfaces, respectively. Futurabond was used following five different protocols: 1) according to the manufacturer's directions, 2) acid etched with 36% phosphoric acid (H3PO4) for 15 seconds, 3) 10% sodium hypochlorite (NaOCl) treated for two minutes after H3PO4-etching, 4) doubling the application time of the adhesive and 5) doubling the number of adhesive coats. Composite build-ups (6 mm in height) were constructed incrementally with Arabesk resin composite. The specimens were stored in 100% humidity for 24 hours at 37 degrees C and sectioned into beams of 1.0 mm2 cross-sectional area. Each beam was tested in tension in an Instron machine at 0.5 mm/minute, and mean microTBS data (MPa) were analyzed by one-way ANOVA and post-hoc multiple comparisons tests (alpha = 0.05). Doubling the application time of Futurabond attained the highest microTBS to dentin; whereas, no differences among all bonding application parameters evaluated could be detected when the adhesive was applied to enamel.

[Pediatric Guillain-Barré syndrome. Experience in the Neuropediatrics Unit of a Portuguese hospital]. / Síndrome de Guillain-Barré en edad pediátrica. Experiencia de la Unidad de Neuropediatría de un hospital portugués.

INTRODUCTION: Guillain-Barré syndrome (GBS) is an acute inflammatory ascending polyradiculoneuropathy. Autoimmune mechanisms play a role in the demyelinating process. Clinically, progressive symmetric loss of motor strength, areflexia, sensitive and autonomic manifestations are observed. Albuminocytological dissociation and electrophysiological signs of demyelination are frequently found. It is the most common cause of acute flaccid paralysis in children. PATIENTS AND METHODS: Retrospective review of all children with GBS admitted to Garcia de Orta Hospital in a 10 year period (1994-2003). RESULTS: 17 children (18 months to 14 years) were admitted during this period. Respiratory or gastrointestinal prodrome was identified in 15 children, with positive serologic studies in six. The main clinical manifestations were disturbances of gait, progressive muscular weakness, sensitive manifestations (pain, paresthesias) and osteotendinous areflexia. 13 children had albuminocytological dissociation and acute demyelinating neuropathy was identified in 12.64% of children were treated with immunoglobulins (2 g/kg). Clinical evolution was favourable in 16 cases, with a death secondary to autonomic dysfunction. CONCLUSIONS: Clinical presentation may be unspecific, particularly in young patients, with pain as a primary complaint, preceding muscular weakness and areflexia. Increased cerebrospinal protein and abnormal electrodiagnostic studies may be absent in the early course of GBS. Immunoglobulin therapy was efficacious and well-tolerated.

Síndrome de Guillain-Barré en edad pediátrica. Experiencia de la Unidad de Neuropediatría de un hospital portugués / Pediatric Guillain-Barré syndrome. Experience in the neuropediatrics unit of a portuguese hospital

Introducción. El síndrome de Guillain-Barré (SGB) es unapolirradiculoneuropatía aguda de naturaleza autoinmune que semanifiesta mediante quejas sensitivas, debilidad muscular progresivasimétrica ascendente y arreflexia. Presenta habitualmente unaumento de la proteinorraquia sin pleiocitosis y los estudios electrofisiológicosdocumentan la existencia de una neuropatía aguda desmielinizantesubyacente. Constituye una urgencia neurológica en laedad pediátrica, y requiere una evaluación y orientación terapéuticaadecuadas. Pacientes y métodos. Estudio retrospectivo de los casosclínicos del SGB admitidos en el Servicio de Pediatría del HospitalGarcia de Orta entre enero de 1994 y diciembre del 2003. Resultados.Durante este período se ingresó a 17 niños, con edades comprendidasentre 18 meses y 14 años. Existió pródomo infeccioso en15 niños, con incremento de los niveles serológicos en seis de ellos.Las manifestaciones clínicas fueron alteraciones de la marcha, disminuciónde la fuerza muscular, manifestaciones sensitivas con predominiodel dolor y arreflexia. La disociación albuminocitológica sedocumentó en 13 niños y se encontraron niveles electrofisiológicosde neuropatía aguda en 12. Se suministró inmunoglobulina endovenosa(2 g/kg) a 11 niños. La evolución clínica fue globalmente favorable,aunque se registró un óbito por disfunción autonómica. Conclusiones.La presentación clínica del SGB puede ser inespecífica alinicio de la enfermedad, especialmente en los grupos de edad másjóvenes, en los que la debilidad muscular y la arreflexia son más difícilesde evaluar. Los exámenes complementarios presentan limitaciones,sobre todo en la primera semana de la enfermedad. El uso deinmunoglobulina fue eficaz y quedó exento de efectos secundariossignificativos

Introduction. Guillain-Barré syndrome (GBS) is an acute inflammatory ascending polyradiculoneuropathy. Autoimmunemechanisms play a role in the demyelinating process. Clinically, progressive symmetric loss of motor strength, arreflexia,sensitive and autonomic manifestations are observed. Albuminocytological dissociation and electrophysiological signs ofdemyelination are frequently found. It is the most common cause of acute flaccid paralysis in children. Patients and methods.Retrospective review of all children with GBS admitted to Garcia de Orta Hospital in a 10 year period (1994-2003). Results.17 children (18 months to 14 years) were admitted during this period. Respiratory or gastrointestinal prodrome was identified in15 children, with positive serologic studies in six. The main clinical manifestations were disturbances of gait, progressivemuscular weakness, sensitive manifestations (pain, paresthesias) and osteotendinous arreflexia. 13 children had albuminocytologicaldissociation and acute demyelinating neuropathy was identified in 12.64% of children were treated with immunoglobulins(2 g/kg). Clinical evolution was favourable in 16 cases, with a death secondary to autonomic dysfunction. Conclusions.Clinical presentation may be unspecific, particularly in young patients, with pain as a primary complaint, preceding muscularweakness and arreflexia. Increased cerebrospinal protein and abnormal electrodiagnostic studies may be absent in the earlycourse of GBS. Immunoglobulin therapy was efficacious and well-tolerated

A critical analysis of on-scene helicopter transport on survival in a statewide trauma system.

BACKGROUND: Recently, questions have been raised regarding the effectiveness of helicopters in trauma care. We conducted a retrospective study to evaluate the effect of on-scene helicopter transport on survival after trauma in a statewide trauma system. METHODS: Data were obtained from a statewide trauma registry of 162,730 patients treated at 28 accredited trauma centers. Patients transported from the scene by helicopter (15,938) were compared with those transported by ground with advanced life support (ALS) (6,473). Interhospital transfers and transports without ALS were excluded. Statistical analysis was performed using one-way analysis of variance and logistic regression. RESULTS: Patients transported by helicopter were significantly (p < 0.01) younger, were more seriously injured, and had lower blood pressure. They were also more likely to be male and to have systolic blood pressure < 90 mm Hg. Logistic regression analysis revealed that when adjusting for other risk factors, transportation by helicopter did not affect the estimated odds of survival. CONCLUSION: A reappraisal of the cost-effectiveness of helicopter triage and transport criteria, when access to ground ALS squads is available, may be warranted.

Organizational and environmental factors in hospital alliance membership and contract management: a resource-dependence perspective.

Using a resource-dependence perspective, we analyze the association between organizational and environmental characteristics and the likelihood that non-profit hospitals will enter into one of two forms of interorganizational relationship (IOR): hospital alliance membership or contract management (n = 1,661). The former is representative of high autonomy IORs, while the latter is representative of low autonomy IORs. Results of logistic regression analysis indicate that hospitals with greater resources and more favorable payer mix are more likely to join alliances, an IOR form which minimizes loss of autonomy. In addition, facilities operating in less favorable environments are more likely to be contract managed and less likely to be alliance members.

Differences in the handling of the EMG examination at seven European laboratories.

This study was undertaken to analyse epidemiological and methodological differences in referral pattern, examination techniques and distribution of diagnoses among different European EMG laboratories. Seven European EMG laboratories filled in questionnaires and sampled 700 cases retrospectively. The use of needle or surface electrodes for nerve studies and the selection of quantitative techniques for muscle studies exhibited considerable variation. The pattern of referral varied with respect to the type of referral source and the neurological expertise of the referring physician. The proportion of patients without any neurophysiological abnormality ranged from 16 to 33%. The 3 most common diagnostic groups were mononeuropathies, polyneuropathies and radiculopathies although a great inter-laboratory variation was found. The proportion of patients with multiple diagnoses varied from 0 to 23% and most of these diagnoses were from a few known combinations. The presence of an inter-laboratory variation suggests that the quality of the EMG examination may be improved by focussing on the use of techniques, strategies and diagnostic criteria.

Influence of inhibition of extraneuronal uptake and of O-methylation on the hyperglycaemia caused by sympathomimetic amines in depancreatized rats.

This study aimed at testing whether the O-methylating system (extraneuronal uptake + O-methylation) modulates, in-vivo, beta-adrenoceptor-mediated responses. The influences of U-0521 (3,4-dihydroxymethylpropiophenone, an inhibitor of catechol-O-methyl transferase (COMT)) and hydrocortisone (an inhibitor of extraneuronal uptake) on the hyperglycaemia evoked by isoprenaline and adrenaline were compared. Both inhibitors enhanced the increase of the plasma glucose level induced by either isoprenaline (0.36 nmol kg-1 min-1) or adrenaline (0.55 nmol kg-1 min-1). The enhancement caused by U-0521 developed faster than that caused by hydrocortisone, but was of the same magnitude. This is the first report of supersensitivity to sympathomimetic amines caused by inhibition of either COMT or extraneuronal uptake in-vivo and for a response not involving smooth muscle cells.

Supersensitivity to catecholamines after inhibition of extraneuronal uptake (uptake2) or O-methylation.

The influence of inhibition of uptake2 and of O-methylation on beta-adrenoceptor-mediated responses of guinea-pig trachea and rat uterus to some catecholamines was compared. The responses were more markedly enhanced by inhibition of O-methylation (by U-0521) than by inhibition of uptake2 (by hydrocortisone). The ranking order for the degree of super-sensitivity caused by either U-0521 or hydrocortisone was different in the two tissues, suggesting differences between the O-methylating systems of those tissues. In experiments with 3H-isoprenaline metabolism, hydrocortisone had a weak inhibitory effect on O-methylation in both tissues.

Hypothermia induces supersensitivity of mouse vas deferens to adrenergic agonists: evidence for postjunctional alpha 2-adrenoceptors.

Hypothermia-induced potentiation of alpha-adrenoceptor-mediated responses of the mouse vas deferens to noradrenaline is mainly caused by inhibition of the sites of loss. However, even after blockade of the sites of loss for noradrenaline or when using methoxamine (which is not a substrate for uptake or metabolism) hypothermia still causes a significant increase in responsiveness. This remaining supersensitivity was shown to be an increased receptor affinity. Furthermore, hypothermia revealed contractile responses to low concentrations of UK 14304 (an alpha 2-agonist).

The guinea-pig trachea O-methylating system is more effective in modulating beta 2- than beta 1-adrenoceptor-mediated responses to isoprenaline.

Assuming that responses of the guinea-pig trachea to isoprenaline in the presence of atenolol (10 mumol L-1) are exclusively, or at least predominantly, beta 2-adrenoceptor mediated and that responses to isoprenaline in the presence of ICI 118,551 (erythro-DL-1(7-methylindan-4-yloxyl)-3-isopropylaminobut an-2-ol) (1 nmol L-1) are exclusively, or at least predominantly beta 1-adrenoceptor mediated, the influence of inhibition of COMT by U-0521 (dehydroxy-2-methyl propiophenone) (50 mumol L-1) has been compared in both conditions. U-0521 enhanced beta 2-adrenoceptor mediated responses to isoprenaline 3.3-fold, while those mediated by beta 1-adrenoceptors were enhanced only 2.2-fold. It is concluded that in guinea-pig trachea COMT activity is functionally more effective in modulating responses which are mediated by beta 2-adrenoceptors than responses mediated by beta 1-adrenoceptors.

The saturability of a site of loss and the degree of supersensitivity to agonists which are substrates of this site of loss.

The present investigation was undertaken to test the hypothesis that the experimentally determined degree of supersensitivity to an agonist caused by inhibition of a site of loss depends on the ratio "Km of the site of loss/ED50 of the agonist". The influence of inhibition of neuronal uptake by cocaine on the alpha-adrenoceptor-mediated effect of noradrenaline was studied on the dog saphenous vein; the influence of inhibition of COMT by U-0521 on the beta-adrenoceptor-mediated effect of isoprenaline was studied on the dog saphenous vein and on the guinea-pig trachea; the influence of inhibition of acetylcholinesterase by physostigmine on the effect of acetylcholine was studied on the guinea-pig ileum. To further extend the range of values of the ratio "Km/ED50", several concentrations of phentolamine, propranolol or atropine were used to "increase the ED50" of the respective agonist. It was thus possible to determine the degree of supersensitivity caused by inhibition of a site of loss over a range of "Km/ED50" values of 0.02 to 2,307. In seven situations the ratio "Km/ED50" was higher than 10. In all of these cases the supersensitivity caused by inhibition of the site of loss was maximal. In eleven situations the ratio "Km/ED50" was less than 10 and higher than 0.1 and the supersensitivity obtained was sub-maximal but was closer to the maximum, the closer the ratio was to 10. In two situations the ratio was less than 0.1 and no supersensitivity was obtained. The results confirm the hypothesis.