Intraoperative bleeding during vitrectomy for diabetic tractional retinal detachment with versus without preoperative intravitreal bevacizumab (IBeTra study)

Aims: To compare the amount of intraoperative intraocular bleeding in patients with diabetes with macula-involving tractional retinal detachment (TRD) undergoing pars plana vitrectomy (PPV) with and without preoperative intravitreal bevacizumab (IVB) injection. Methods: An institutional study was carried out with consecutive patients with diabetic retinopathy and macula-involving TRD of recent (3 months) onset who were randomly assigned to PPV only (PPV group) or PPV combined with one IVB (1.5 mg/0.06 ml) injection 2 weeks prior to surgery (bevacizumab (BEV)/PPV group). All patients underwent 23-gauge PPV 3 weeks after baseline. The main outcome measure was erythrocyte count in the fluid retrieved from the vitrectomy cassette using a Neubauer counting chamber. Results: The study included 20 patients. The mean erythrocyte count was 14865x10(3) (SD 19332x10(3); median 4500x10(3)) cells in the BEV/PPV group, and 176240x10(3) (SD 108375x10(3); median 166600x10(3)) cells in the PPV group. The mean erythrocyte count was significantly lower in the BEV/PPV group than in the PPV group (p < 0.0001). No major adverse events were identified. Conclusion: Preoperative IVB injection was associated with reduced intraocular bleeding during 23-gauge PPV for diabetic macula-involving TRD. Further studies are needed to confirm our preliminary findings.

Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study)

Background/aims: The aim of this study was to compare the morphological and visual acuity outcomes associated with a single intravitreal injection of triamcinolone acetonide versus bevacizumab for the treatment of refractory diffuse diabetic macular oedema. Methods: Twenty-eight patients were randomly assigned to receive a single intravitreal injection of either 4 mg/0.1 ml triamcinolone acetonide or 1.5 mg/0.06 ml bevacizumab. Comprehensive ophthalmic evaluation was performed at baseline and at weeks 1, 4, 8 (+/- 1), 12 (+/- 2) and 24 (+/- 2) after treatment. Main outcome measures included central macular thickness measured with optical coherence tomography (OCT) and best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. Results: Twenty-six patients (26 eyes) completed all study visits (two patients missed two consecutive study visits). Central macular thickness was significantly reduced in the intravitreal triamcinolone group compared with the bevacizumab group at weeks 4, 8, 12 and 24 (p<0.05). Logarithm of the minimum angle of resolution (LogMAR) best-corrected visual acuity was significantly higher at weeks 8 (0.69; similar to 20/100(+1)) and 12 (0.74; 20/100(-2)) in the intravitreal triamcinolone group compared with the bevacizumab group (weeks 8 (0.83; similar to 20/125(-1)) and 12 (0.86; 20/ 160(+2))) (p<0.05). Significant change from baseline in mean intraocular pressure (mmHg) was seen at week 4 (+2.25) only in the intravitreal triamcinolone group (p<0.0001). No patient had observed cataract progression during the study. Conclusions: One single intravitreal injection of triamcinolone may offer certain advantages over bevacizumab in the short-term management of refractory diabetic macular oedema, specifically with regard to changes in central macular thickness. The actual clinical relevance of our preliminary findings, however, remains to be determined in future larger studies.

OCT findings in macular hole formation in eyes with complete vitreofoveal separation

The current study describes the morphologic macular features in two eyes that developed full-thickness macular holes in the setting of documented vitreofoveal separation. Using third-generation optical coherence tomography, complete vitreofoveal separation associated with the disruption of the inner foveal retina was documented in both cases. Five months after presentation, decreased vision and epiretinal membrane formation associated with development of a full-thickness macular hole were observed in the first patient. In the second patient, a full-thickness macular hole was demonstrated by optical coherence tomography 6 weeks after presentation. These findings suggest that full-thickness macular holes may develop in eyes with vitreofoveal separation. Evidence of the disturbance of the inner foveal architecture on optical coherence tomography indicates the potential role of factors other than anteroposterior or oblique vitreoretinal tractional forces in the genesis of some full-thickness macular holes.

INTRAVITREAL INJECTION OF AUTOLOGOUS BONE MARROW-DERIVED MONONUCLEAR CELLS FOR HEREDITARY RETINAL DYSTROPHY A Phase I Trial

Purpose: To evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa or cone-rod dystrophy. Methods: A prospective, Phase I, nonrandomized, open-label study including 3 patients with retinitis pigmentosa and 2 patients with cone-rod dystrophy and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/200 or worse. Evaluations including best-corrected visual acuity, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography, and optical coherence tomography were performed at baseline and 1, 7, 13, 18, 22, and 40 weeks after intravitreal injection of 10 X 10(6) autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient. Results: No adverse event associated with the injection was observed. A 1-line improvement in best-corrected visual acuity was measured in 4 patients 1 week after injection and was maintained throughout follow-up. Three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave amplitude approximately 35 mu V), which remained recordable throughout follow-up, and 1 patient showed a small response (a wave amplitude approximately 20 mu V) recordable only at Weeks 7, 13, 22, and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on optical coherence tomography or fluorescein and indocyanine green angiograms. Conclusion: Intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced retinitis pigmentosa or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. Further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies. RETINA 31: 1207-1214, 2011

Genetic associations between age at first calving and heifer body weight and scrotal circumference in Nelore cattle

P>Age at first calving (AFC) measures the entry of heifers into the beef cattle production system. This trait can be used as a selection criterion for earlier reproductive performance. Using data from Nelore cattle participating in the `Program for Genetic Improvement of the Nelore Breed` (PMGRN-Nelore Brazil), bi-trait analyses were performed using the restricted maximum likelihood method, based on an AFC animal model and the following traits: female body weight adjusted to 365 (BW365) and 450 (BW450) days of age, and male scrotal circumference adjusted to 365 (SC365), 450 (SC450), 550 (SC550) and 730 (SC730) days of age. The heritability estimates for AFC ranged from 0.02 +/- 0.02 to 0.04 +/- 0.02. The estimates of additive direct heritabilities (with standard error) for BW365, BW450, SC365, SC450, SC550 and SC730 were 0.36 +/- 0.07, 0.38 +/- 0.07, 0.48 +/- 0.07, 0.65 +/- 0.07, 0.64 +/- 0.07 and 0.42 +/- 0.07, respectively, and the genetic correlations with AFC were -0.38, -0.33, 0.10, -0.13, -0.13 and 0.06, respectively. In the herds studied, selection for SC365, SC450, SC550 or SC730 should not cause genetic changes in AFC. Selection based on BW365 or BW450 would favor smaller AFC breeding values. However, the low magnitude of direct heritability estimates for AFC in these farms indicates that changes in phenotypical expression depend mostly on non-genetic factors.

Pain and distress reactivity and recovery as early predictors of temperament in toddlers born preterm

Background: Pain reactivity may reflect underlying mechanisms of constitutional aspects of temperament. Aim: To examine whether the neonatal biobehavioral reactivity and recovery responses from pain and distress, as well as the gestational age, the illness severity and the amount of painful procedures undergone the Neonatal Intensive Care Unit (NICU) stay, predict temperament later in toddlerhood, in vulnerable children born preterm. Study design: Prospective-longitudinal study. Subjects: Twenty-six preterm and very low birth weight infants followed from birth to toddlerhood. Outcome measures: Illness severity was assessed with the Clinical Risk Index for Babies (CRIB) score. The medical charts were reviewed prospectively for obtaining the amount of pain exposure in NICU. For assessing the behavioral and cardiac reactivity and recovery from pain and distress, the neonates were evaluated during routine blood collection in the NICU in the first 10 days of life. Pain and distress reactivity and recovery was measured using the Neonatal Facial Coding System score, the duration of crying. and the magnitude of average heart rate. At toddlerhood, mothers answered the Early Childhood Behavior Questionnaire. Results: Higher biobehavioral reactivity to pain and distress predicted higher temperamental Negative Affect, above and beyond gestational age, illness severity and amount of pain exposure in NICU. However, we did not find a predictive relation between gestational age, CRIB score and number of painful procedures undergone NICU and toddler`s temperament. Conclusions: The findings highlight the relevance of the neonatal individual characteristics of reactivity for identifying more vulnerable infants for future problems in biobehavioral regulation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Influence of enzyme inducing antiepileptic drugs on the pharmacokinetics of levetiracetam in patients with epilepsy

To assess whether levetiracetam elimination is influenced by enzyme inducing antiepileptic drugs (EIAEDs), serum levetiracetam levels were determined at frequent intervals after a single oral 1000 mg dose in 15 subjects co-medicated with EIAEDs and 15 matched controls. The EIAED group showed a higher levetiracetam oral clearance (p = 0.01) and a shorter half-life (p = 0.02) than controls. Although the magnitude of interaction is relatively modest, it could have clinical significance for some patients. (C) 2011 Elsevier B.V. All rights reserved.

Hypertrophy and neuron loss: structural changes in sheep SCG induced by unilateral sympathectomy

Recently, superior cervical ganglionectomy has been performed to investigate a variety of scientific topics from regulation of intraocular pressure to suppression of lingual tumour growth. Despite these recent advances in our understanding of the functional mechanisms underlying superior cervical ganglion (SCG) growth and development after surgical ablation, there still exists a need for information concerning the quantitative nature of the relationships between the removed SCG and its remaining contralateral ganglion and between the remaining SCG and its modified innervation territory. To this end, using design-based stereological methods, we have investigated the structural changes induced by unilateral ganglionectomy in sheep at three distinct timepoints (2, 7 and 12 weeks) after surgery. The effects of time, and lateral (left-right) differences, were examined by two-way analyses of variance and paired t-tests. Following removal of the left SCG, the main findings were: (i) the remaining right SCG was bigger at shorter survival times, i.e. 74% at 2 weeks, 55% at 7 weeks and no increase by 12 weeks, (ii) by 7 weeks after surgery, the right SCG contained fewer neurons (no decrease at 2 weeks, 6% fewer by 7 weeks and 17% fewer by 12 weeks) and (iii) by 7 weeks, right SCG neurons were also larger and the magnitude of this increase grew substantially with time (no rise at 2 weeks, 77% by 7 weeks and 215% by 12 weeks). Interaction effects between time and ganglionectomy-induced changes were significant for SCG volume and mean perikaryal volume. These findings show that unilateral superior cervical ganglionectomy has profound effects on the contralateral ganglion. For future investigations, it would be interesting to examine the interaction between SCGs and their innervation targets after ganglionectomy. Is the ganglionectomy-induced imbalance between the sizes of innervation territories the milieu in which morphoquantitative changes, particularly changes in perikaryal volume and neuron number, occur? Mechanistically, how would those changes arise? Are there any grounds for believing in a ganglionectomy-triggered SCG cross-innervation and neuroplasticity? (C) 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Genotyping of Toxoplasma gondii isolates from free range chickens in the Pantanal area of Brazil

The aim of this paper was to genetically characterize Toxoplasma gondii isolates from free range chickens in regions of Brazilian territory in the state of Mato Grosso do Sul (MS) where T. gondii strains have never been studied. In total, T. gondii isolates from 22 free range chickens were included in this study. Fifty chickens from Eldorado, thirty from Rio Verde and ten from Aquidauana were sampled between January and April 2007. In relation to the genetic diversity of T. gondii isolates from chickens in MS, the magnitude of the diversity in the isolates sampled in this study was comparable to the overall diversity in a composite data set. These 22 isolates in MS revealed 11 genotypes, whereas the 321 isolates ever genotyped in Brazil have revealed 95 genotypes. The values of Simpson`s Diversity Index for the whole population of T. gondii isolates in Brazil, the whole population of T. gondii isolates from chickens in Brazil and the population surveyed in this study were 0.97, 0.95 and 0.90, respectively. Seven of the 11 genotypes revealed from chicken isolates from MS are newly described genotypes and six of them each have a single isolate. In conclusion, the results obtained from isolates in MS corroborate previous studies on T. gondii isolates in Brazil, thus confirming their diversity and atypicality. Nonetheless, the applicability of PCR-RFLP markers for epidemiological inferences remains controversial. (c) 2011 Elsevier B.V. All rights reserved.

Estimation of R(0) from the initial phase of an outbreak of a vector-borne infection

The magnitude of the basic reproduction ratio R(0) of an epidemic can be estimated in several ways, namely, from the final size of the epidemic, from the average age at first infection, or from the initial growth phase of the outbreak. In this paper, we discuss this last method for estimating R(0) for vector-borne infections. Implicit in these models is the assumption that there is an exponential phase of the outbreaks, which implies that in all cases R(0) > 1. We demonstrate that an outbreak is possible, even in cases where R(0) is less than one, provided that the vector-to-human component of R(0) is greater than one and that a certain number of infected vectors are introduced into the affected population. This theory is applied to two real epidemiological dengue situations in the southeastern part of Brazil, one where R(0) is less than one, and other one where R(0) is greater than one. In both cases, the model mirrors the real situations with reasonable accuracy.

Evaluation of albuminuria and its relationship with blood pressure in dogs with chronic kidney disease

Background Microalbuminuria and hypertension have long been associated with a guarded prognosis in human patients with a variety of diseases. In veterinary medicine, tests for microalbuminuria have been used for detecting early kidney damage, but there is little information regarding its association with high blood pressure in dogs with chronic kidney disease (CKD). Objective The objective of this study was to evaluate albuminuria and its association with arterial hypertension in dogs with CKD. Methods Urinary albumin:creatinine (UAC) ratio, urinary protein:creatinine (UPC) ratio, and systolic blood pressure were determined in 39 clinically healthy dogs and 40 dogs with CKD. Results UAC in dogs with CKD (range, 0.002-7.99; median, 0.38) was statistically different from that of control dogs (range, 0.0005-0.01; median, 0.002). Microalbuminuria (UAC 0.03-0.3) and macroalbuminuria (UAC > 0.3) were detected in 32.5% and 50% of dogs with CKD, respectively. Sixty percent (24/40) of dogs with CKD had systolic pressure >= 180 mmHg; in these dogs, UAC ratio (range, 0.006-7.99; median, 1.72) was significantly higher than in dogs with CKD and systolic pressure < 180 mmHg (range, 0.002-4.83; median, 0.10). Of hypertensive dogs with CKD, those with UPC > 1.0 usually had macroalbuminuria, those with UPC 0.5-1.0 usually had microalbuminuria, and those with UPC < 0.5 usually lacked albuminuria. Conclusions UAC ratio was higher in hypertensive than in normotensive dogs with CKD. Tests designed to detect microalbuminuria may be useful for hypertensive dogs with CKD and a UPC < 1.0 to detect the onset and magnitude of albuminuria. Once macroalbuminuria is overt, the UPC ratio itself can be used for the same purpose.

Insulin-like growth factor-1 protects preimplantation embryos from anti-developmental actions of menadione

Menadione is a naphthoquinone used as a vitamin K source in animal feed that can generate reactive oxygen species (ROS) and cause apoptosis. Here, we examined whether menadione reduces development of preimplantation bovine embryos in a ROS-dependent process and tested the hypothesis that actions of menadione would be reduced by insulin-like growth factor-1 (IGF-1). Menadione caused a concentration-dependent decrease in the proportion of embryos that became blastocysts. All concentrations tested (1, 2.5, and 5.0 mu M) inhibited development. Treatment with 100 ng/ml IGF-1 reduced the magnitude of the anti-developmental effects of the two lowest menadione concentrations. Menadione also caused a concentration-dependent increase in the percent of cells positive for the TUNEL reaction. The response was lower for IGF-1-treated embryos. The effects of menadione were mediated by ROS because (1) the anti-developmental effect of menadione was blocked by the antioxidants dithiothreitol and Trolox and (2) menadione caused an increase in ROS generation. Treatment with IGF-1 did not reduce ROS formation in menadione-treated embryos. In conclusion, concentrations of menadione as low as 1.0 mu M can compromise development of bovine preimplantation embryos to the blastocyst stage of development in a ROS-dependent mechanism. Anti-developmental actions of menadione can be blocked by IGF-1 through effects downstream of ROS generation.

Visitor profiles and environmental attributes, especially of birds, attracting visitors to Lamington National Park: Tourist attitudes and economic issues

Uses a sample of 622 day and overnight visitors to the O’ Reilly’s/Green Mountains site of Lamington National Park, Queensland, Australia, to identify their socio-economic and other pertinent characteristics and the main reasons and attributes that attract them to the site. Particular attention is given to birds and their attributes as attractions. The primary economic injection accruing locally as a result of visits is examined and the difference that the presence of birds makes to local expenditure by visitors is explored. The extent of support for and objection to the introduction of a fee for entering Lamington National Park is estimated. The many suggestions received from visitors for environmental improvements at this site are discussed. It is suggested that unless a way can be found to regulate the number of visitors to this site and obtain extra funds to finance improvements at this site, the magnitude of many of these problems will grow. This will necessitate a fresh look at the desirability or otherwise for charging entry fees to Lamington National Park.

Elastic modulus of posts and the risk of root fracture

The definition of an optimal elastic modulus for a post is controversial. This work hypothesized that the influence of the posts` elastic modulus on dentin stress concentration is dependent on the load direction. The objective was to evaluate, using finite element analysis, the maximum principal stress (sigma(max)) on the root, using posts with different elastic modulus submitted to different loading directions. Nine 3D models were built, representing the dentin root, gutta-percha, a conical post and the cortical bone. The softwares used were: MSC.PATRAN2005r2 (preprocessing) and MSC.Marc2005r2 (processing). Load of 100 N was applied, varying the directions (0 degrees, 45 degrees and 90 degrees) in relation to the post`s long axis. The magnitude and direction of the sigma(max) were recorded. At the 45 degrees and 90 degrees loading, the highest values of sigma(max) were recorded for the lowest modulus posts, on the cervical region, with a direction that suggests debonding of the post. For the 0 degrees loading, the highest values of sigma(max) were recorded for higher modulus posts, on the apical region, and the circumferential direction suggests vertical root fracture. The hypothesis was accepted: the effect of the elastic modulus on the magnitude and direction of the sigma(max) generated on the root was dependent on the loading direction.

The suitability of different FEA models for studying root fractures caused by wedge effect

Finite element analysis (FEA) utilizing models with different levels of complexity are found in the literature to study the tendency to vertical root fracture caused by post intrusion (""wedge effect""). The objective of this investigation was to verify if some simplifications used in bi-dimensional FEA models are acceptable regarding the analysis of stresses caused by wedge effect. Three plane strain (PS) and two axisymmtric (Axi) models were studied. One PS model represented the apical third of the root entirely, in dentin (PS-nG). The other models included gutta-percha in the apical third, and differed regarding dentin-post relationship: bonded (PS-B and Axi-B) or nonbonded (PS-nB and Axi-nB). Mesh discretization and material properties were similar for all cases. Maximum principal stress (sigma(max)) was analyzed as a response to a 165 N longitudinal load. Stress magnitude and orientation varied widely (PS-nG: 10.3 MPa; PS-B: 0.8 MPa; PS-nB: 10.4 MPa; Axi-13: 0.2 MPa, Axi-nB: 10.8 MPa). Axi-nB was the only model where all (sigma(max) vectors at the apical third were perpendicular to the model plane. Therefore, it is adequate to demonstrate the tendency to vertical root fractures caused by wedge effect. Axi-13 showed only part of the (sigma(max) perpendicular to the model plane while PS models showed sigma(max) on the model plane. In these models, sigma(max) orientation did not represent a situation where vertical root fracture would occur due to wedge effect. Adhesion between post and dentin significantly reduced (c) 2007 Wiley Periodicals, Inc.