Glial cell line-derived neurotrophic factor added to a sciatic nerve fragment grafted in a spinal cord gap ameliorates motor impairments in rats and increases local axonal growth

Purpose: The aversive nature of regenerative milieu is the main problem related to the failure of neuronal restoration in the injured spinal cord which however might be addressed with an adequate repair intervention. We evaluated whether glial cell line-derived neurotrophic factor (GDNF) may increase the ability of sciatic nerve graft, placed in a gap promoted by complete transections of the spinal cord, to enhance motor recovery and local fiber growth. Methods: Rats received a 4 mm-long gap at low thoracic level and were repaired with a fragment of the sciatic nerve. GDNF was added (NERVE+GDNF) or not to the grafts (NERVE-GDNF). Motor behavior score (BBB) and sensorimotor tests-linked to the combined behavior score (CBS), which indicate the degree of the motor improvement and the percentage of functional deficit, respectively, and also the spontaneous motor behavior in an open field by means of an infrared motion sensor activity monitor were analyzed. At the end of the third month post surgery, the tissue composed by the graft and the adjacent regions of the spinal cord was removed and submitted to the immunohistochemistry of the neurofilament-200 (NF-200), growth associated protein-43 (GAP-43), microtubule associated protein-2 (MAP-2), 5-hidroxytryptamine (serotonin, 5-HT) and calcitonin gene related peptide (CGRP). The immunoreactive fibers were quantified at the epicenter of the graft by means of stereological procedures. Results: Higher BBB and lower CBS levels (p < 0.001) were found in NERVE+GDNF rats. GDNF added to the graft increased the levels of individual sensorimotor tests mainly at the third month. Analysis of the spontaneous motor behavior showed decreases in the time and number of small movement events by the third month without changes in time and number of large movement events in the NERVE+GDNF rats. Immunoreactive fibers were encountered inside the grafts and higher amounts of NF-200, GAP-43 and MAP-2 fibers were found in the epicenter of the graft when GDNF was added. A small amount of descending 5-HT fibers was seen reentering in the adjacent caudal levels of the spinal cords which were grafted in the presence of GDNF, event that has not occurred without the neurotrophic factor. GDNF in the graft also led to a large amount of MAP-2 perikarya and fibers in the caudal levels of the cord gray matter, as determined by the microdensitometric image analysis. Conclusions: GDNF added to the nerve graft favored the motor recovery, local neuronal fiber growth and neuroplasticity in the adjacent spinal cord.

Long-Term Astroglial Reaction and Neuronal Plasticity in the Subcortical Visual Pathways After a Complete Ablation of Telencephalon in Pigeons (Columba livia)

This paper analyzes the astroglial and neuronal responses in subtelencephalic structures, following a bilateral ablation of the telencephalon in the Columba livia pigeons. Control birds received a sham operation. Four months later the birds were sacrificed and their brains processed for glial fribillary acid protein (GFAP) and neurofilament immunohistochemistry, markers for astrocytes and neurons, respectively. Computer-assisted image analysis was employed for quantification of the immunoreactive labeling in the nucleus rotundus (N.Rt) and the optic tectum (OT) of the birds. An increased number of GFAP immunoreactive astrocytes were found in several subregions of the N.Rt (p .001), as well as in layers 1, 2cd, 3, and 6 of the OT (p .001) of the lesioned animals. Neurofilament immunoreactivity decreased massively in the entire N.Rt of the lesioned birds; however, remaining neurons with healthy aspect showing large cytoplasm and ramified branches were detected mainly in the periphery of the nucleus. In view of the recently described paracrine neurotrophic properties of the activated astrocytes, the data of the present study may suggest a long-lasting neuroglial interaction in regions of the lesioned bird brain far from injury. Such events may trigger neuronal plasticity in remaining brain structures that may lead spontaneous behavior recovery as the one promoted here even after a massive injury.

Speech Evaluation After Palatal Augmentation in Patients Undergoing Glossectomy

Objective: To assess, in patients undergoing glossectomy, the influence of the palatal augmentation prosthesis on the speech intelligibility and acoustic spectrographic characteristics of the formants of oral vowels in Brazilian Portuguese, specifically the first 3 formants (F1 [/a,e,u/], F2 [/o,o,u/], and F3 [/a,o/]). Design: Speech evaluation with and without a palatal augmentation prosthesis using blinded randomized listener judgments. Setting: Tertiary referral center. Patients: Thirty-six patients (33 men and 3 women) aged 30 to 80 (mean [SD], 53.9 [10.5]) years underwent glossectomy (14, total glossectomy; 12, total glossectomy and partial mandibulectomy; 6, hemiglossectomy; and 4, subtotal glossectomy) with use of the augmentation prosthesis for at least 3 months before inclusion in the study. Main Outcome Measures: Spontaneous speech intel-ligibility (assessed by expert listeners using a 4-category scale) and spectrographic formants assessment. Results: We found a statistically significant improvement of spontaneous speech intelligibility and the average number of correctly identified syllables with the use of the prosthesis (P < .05). Statistically significant differences occurred for the F1 values of the vowels /a,e,u/; for F2 values, there was a significant difference of the vowels /o,o,u/; and for F3 values, there was a significant difference of the vowels la,61 (P < .001). Conclusions: The palatal augmentation prosthesis improved the intelligibility of spontaneous speech and syllables for patients who underwent glossectomy. It also increased the F2 and F3 values for all vowels and the F I values for the vowels /o,o,u/. This effect brought the values of many vowel formants closer to normal.

Risk Factors for Visual Field Progression in Treated Glaucoma

Objective: To determine intraocular pressure (IOP)-dependent and IOP-independent variables associated with visual field (VF) progression in treated glaucoma. Design: Retrospective cohort of the Glaucoma Progression Study. Methods: Consecutive, treated glaucoma patients with repeatable VF loss who had 8 or more VF examinations of either eye, using the Swedish Interactive Threshold Algorithm (24-2 SITA-Standard, Humphrey Field Analyzer II; Carl Zeiss Meditec, Inc, Dublin, California), during the period between January 1999 and September 2009 were included. Visual field progression was evaluated using automated pointwise linear regression. Evaluated data included age, sex, race, central corneal thickness, baseline VF mean deviation, mean follow-up IOP, peak IOP, IOP fluctuation, a detected disc hemorrhage, and presence of beta-zone parapapillary atrophy. Results: We selected 587 eyes of 587 patients (mean [SD] age, 64.9 [13.0] years). The mean (SD) number of VFs was 11.1 (3.0), spanning a mean (SD) of 6.4 (1.7) years. In the univariable model, older age (odds ratio [OR], 1.19 per decade; P = .01), baseline diagnosis of exfoliation syndrome (OR, 1.79; P = .01), decreased central corneal thickness (OR, 1.38 per 40 mu m thinner; P < .01), a detected disc hemorrhage (OR, 2.31; P < .01), presence of beta-zone parapapillary atrophy (OR, 2.17; P < .01), and all IOP parameters (mean follow-up, peak, and fluctuation; P < .01) were associated with increased risk of VF progression. In the multivariable model, peak IOP (OR, 1.13; P < .01), thinner central corneal thickness (OR, 1.45 per 40 mu m thinner; P < .01), a detected disc hemorrhage (OR, 2.59; P < .01), and presence of beta-zone parapapillary atrophy (OR, 2.38; P < .01) were associated with VF progression. Conclusions: IOP-dependent and IOP-independent risk factors affect disease progression in treated glaucoma. Peak IOP is a better predictor of progression than is IOP mean or fluctuation.

Development of an animal model for endometrial ablation using trichloroacetic acid

Objective: To develop an animal model of endometrial ablation, and to evaluate the histologic effects of trichloroacetic acid (TCA) in the uterine cavity. Design: Experimental prospective. Setting: Department of gynecology. Patient(s): Thirty female adult rats. Intervention(s): Animals were submitted to injection of TCA in one uterine horn and saline solution in the other. Group 1 was sacrificed the day after the procedure. Group 2 was sacrificed in phase of diestrus. Superficial epithelia of the endometrium, stromal thickness, endometrial glands, and myometrium thickness were compared among the uterine horns of the same rats of group 1. The same evaluation was performed in group 2. Endometrial regeneration was evaluated. Main Outcome Measure(s): Histologic effects. Result(s): In group 1, histologic parameters showed endometrial destruction on TCA injected uterine horn. In group 2, four rats died after the procedure, and six rats had no viable material. In the rest of the group, TCA-injected uterine horns showed endometrial destruction. Superficial epithelia of the endometrium and stromal thickness were similar between TCA uterine horn from groups. However, the number of endometrial glands was higher in group 1. Conclusion(s): The study developed an experimental model for endometrial ablation. TCA acid is a potent agent for endometrial ablation in rat model. No endometrial regeneration was observed after recovery of cycle. (Fertil Steril (R) 2011; 95: 2418-21. (C) 2011 by American Society for Reproductive Medicine.)

Vascular endothelial growth factor and beta-human chorionic gonadotropin are associated with trophoblastic invasion into the tubal wall in ectopic pregnancy

Objective: To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and beta-hCG and to assess its predictive value. Design: Prospective study. Setting: Tertiary care university hospital. Patient(s): Thirty patients with ampullary pregnancy undergoing salpingectomy were analyzed. Intervention(s): Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer, and stage III in the case of complete tubal wall infiltration. Main Outcome Measure(s): The relation between depth of trophoblastic infiltration into the tubal wall with VEGF and beta-hCG serum concentrations on the day of surgery. Result(s): An association between the depth of trophoblastic invasion and maternal serum concentrations of VEGF and beta-hCG was observed. VEGF levels of 297.2 pg/mL showed 100.0% sensitivity and 90.0% specificity for stage I, and levels of 440.1 pg/mL showed 81.8% sensitivity and 88.8% specificity for stage III. Beta-hCG levels of 2590.0 mIU/mL showed 88.9% sensitivity and 80.0% specificity for stage I, and levels of 10,827.0 mUI/mL showed 72.7% sensitivity and 88.9% specificity for stage III. Conclusion(s): Maternal serum VEGF and beta-hCG concentrations are associated with depth of trophoblastic penetration into the tubal wall. (Fertil Steril (R) 2010;94:1595-600. (C) 2010 by American Society for Reproductive Medicine.)

Two-stage transvaginal cervical length screening for preterm birth in twin pregnancies

Aim: To compare cervical length (CL) at 18-21 and 22-25 weeks` gestation in twin pregnancies in prediction of spontaneous preterm delivery and to examine cervical shortening. Methods: Retrospective cohort study of CL measured at 18-21 and 22-25 weeks` gestation in twin pregnancies. Results: Receiver operating characteristics (ROC) curve revealed area of 0.64 (95% CI 0.53-0.75) and 0.80 (95% CI 0.72-0.88) for measurements at 18-21 and 22-25 weeks, respectively (P <= 0.001). Sensitivities of 33.3% and 23% and negative predicting value (NPV) of 97.3% and 86.8% for delivery at <28 and <34 weeks gestation were reached for measurements at 18-21 weeks. Sensitivities of 71.4% and 38.2% and NPV of 99.1% and 91.4% for delivery at <28 and <34 weeks` gestation were reached for measurements at 22-25 weeks. Cervical length shortening analysis showed an area under ROC curve of 0.81 (95% CI 0.73-0.89) and best cut-off was at >= 2 mm/week. Sensitivities of 80% and 60.8% and NPV of 98.9% and 90.6% for delivery at <28 and <34 weeks gestation were reached. Conclusions: In twin gestations, assessment of CL at 22-25 weeks is better than assessment at 18-21 weeks to predict preterm delivery before 34 weeks. Cervical shortening at a rate of >= 2 mm/weeks between 18 and 25 weeks gestation was a good predictor of spontaneous preterm birth in this high-risk population.

Prematurity prevention: the role of progesterone

Purpose of review This review summarizes the evidence of the effectiveness of progesterone on the rate of preterm birth and evaluates the most recent studies. Recent findings The incidence of preterm delivery is about 7-11% of all pregnant women and preterm birth is one of the most important causes of neonatal morbidity and mortality. Interventions to reduce such complications have been attempted for several years. Most efforts so far have been tertiary interventions, such as treatment with antenatal corticosteroids, tocolytic agents, and antibiotics. Some of these measures have reduced perinatal morbidity and mortality, but the incidence of preterm birth is increasing. Recently, researches have suggested prophylactic progesterone could reduce the preterm birth rate in a select group presenting previous preterm birth and a short cervical length by transvaginal scan at mid-trimester pregnancy. Summary This review intends to define the current indication for administration of progesterone for pregnant women. On the basis of current knowledge, progesterone should be offered to women with a documented history of a previous spontaneous birth at less than 37 weeks and for those found to have a short cervical length of 15 mm or less. Studies are needed to evaluate progesterone efficacy on other risk factors.

Estrogen effects on pilocarpine-induced temporal lobe epilepsy in rats

Objetive: To evaluate the effects of conjugated equine estrogens (CEE) on the pilocarpine-induced epilepsy in rats. Study design: 40 female rats were divided into: GPC (positive control) presented ""status epilepticus"" (SE) induced by pilocarpine; GOC(ovariectomized control) only castrated; GNC (negative control) received only saline solution; GPE received pilocarpine, presented SE, castrated and received 50 mu g/kg CEE treatment; GPV received pilocarpine, castrated and received propylene glycol (vehicle). The animals were monitored by a video system. At the end of observation, the brains removed for later histologic analysis using Neo-Timm and Nissl methods. Results: The GPE presented a reduction in number of seizures compared to GPV. The Neo-Timm analysis showed that GPV had greater sprouting of mossy fibers, with a denser band in the area of the dentate gyrus hilum compared to GPE. On Nissl staining, GPE showed evident neuronal loss in the CA3 area. GPV presented loss in CA1 and dentate gyrus. Conclusion: Estrogen may have a protecting effect on the central nervous system. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Ductus venosus Doppler and postnatal outcomes in fetuses with absent or reversed end-diastolic flow in the umbilical arteries

Objective: To evaluate the relationship between ductus venosus Doppler findings on the day of delivery and postnatal outcomes in pregnancies with absent or reversed end-diastolic (ARED) flow in the umbilical arteries. Study design: Postnatal outcomes of 103 newborns of pregnancies with a diagnosis of ARED flow on Doppler velocimetry of the umbilical arteries were analyzed retrospectively between January 1997 and December 2004. Single pregnancies and fetuses without malformations were included. The cases were divided into two groups according to the flow during atrial contraction (a-wave) in the ductus venosus on the day of delivery: group A, 20 cases with absent or reversed flow in the ductus venosus and group B, 83 cases with positive flow. The results were analyzed statistically using the chi-square test, Fisher`s exact test and the Mann-Whitney U test with the level of significance set at 5%. Results: All newborns were delivered by cesarean section. Gestational age was similar in the two groups (group A: 30 weeks and group B: 30.9 weeks, P = 0.23). Absent or reversed ductus venosus flow was associated with the following adverse postnatal outcomes: lower birthweight (P < 0.001), lower Apgar scores in the first (P = 0.001) and fifth minute (P = 0.001), a higher frequency of orotracheal intubation (P = 0.001) and pH at birth less than 7.20 (P < 0.001), pulmonary hemorrhage (P = 0.03), thrombocytopenia (P = 0.02), hypoglycemia (P = 0.01), intracranial hemorrhage (P = 0.02), and postnatal death (P = 0.007). Conclusion: The study of ductus venosus flow may provide additional information regarding the best time for interruption of pregnancies with ARED flow in the umbilical arteries characterized by extreme prematurity. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

MENISCAL INJURY DUE TO FATIGUE

Objective: The purpose of the present study was to review a group of patients with meniscal injuries resulting from structural failure unrelated to trauma or degenerative problems to which was given the name ""meniscal injury due to fatigue"". Material and Method: Evaluations were made on 140 patients with meniscal injuries without any apparent cause, who were therefore considered to have meniscal injuries due to fatigue. Among these, 85 patients were male and 55 were female. The medial meniscus was the most affected site (92% of the cases). Results: All these injuries were diagnosed by means of clinical examination and magnetic resonance imaging. The patients underwent meniscectomy by means of arthroscopy and the results were divided into two types: good and poor. Poor results were found in 27% of the cases, among which nine patients progressed to idiopathic osteonecrosis. Conclusion: We conclude that injuries due to fatigue must be assessed as injuries caused by failure and, therefore, constituting a syndromic pathological condition that may progress to idiopathic osteonecrosis.

Potentializing the effects of GM1 by hyperbaric oxygen therapy in acute experimental spinal cord lesion in rats

Study design: Experimental, controlled, animal study. Objectives: To evaluate the effect of GM1 ganglioside, hyperbaric oxygen and both in combination, in the treatment of experimental spinal cord lesions in rats. Setting: Brazil. Methods: Thirty-two Wistar rats with spinal cord lesions were divided into four groups: one group received GM1 ganglioside, one was submitted to hyperbaric oxygen therapy (HBOT), the third received both treatments and the fourth received no treatment (control). Results: There were no significant differences between the groups in the histological analysis, for any of the variables (necrosis, hemorrhage, hyperemia, cystic degeneration, P>0.06). Neither were there any significant differences in the comparison of left and right sides in the functional tests (P>0.06 for all). No significant differences were found in the locomotor ratings, in the comparison of groups at 2, 7, 21 and 28 days after the surgical procedure. However, in the evaluation on day 14, group 3, which received the combined therapy, showed a significantly higher Basso Beattie and Bresnahan score than the other groups (P = 0.015). Conclusion: The therapeutic effect of GM1 in locomotor evaluation of rats submitted to spinal cord lesion is anticipated by HBOT. Spinal Cord (2010) 48, 808-813; doi:10.1038/sc.2010.37; published online 27 April 2010

Paternal and maternal ages at conception and risk of bipolar affective disorder in their offspring

Background. A consistent association between paternal age and their offspring`s risk of schizophrenia has been observed, with no independent association with maternal age. The relationship of paternal and maternal ages with risk of bipolar affective disorders (BPAD) in the offspring is less clear. The present study aimed at testing the hypothesis that paternal age is associated with their offspring`s risk of BPAD, whereas maternal age is not. Method. This population-based cohort study was conducted with individuals born in Sweden during 1973-1980 and still resident there at age 16 years. Outcome was first hospital admission with a diagnosis of BPAD. Hazard ratios (HRs) were calculated using Cox`s proportional hazard regression. Results. After adjustment for all potential confounding variables except maternal age, the HR for risk of BPAD for each 10-year increase in paternal age was 1.28 [95% confidence interval (Cl) 1.11-1.48], but this fell to 1.20 (95% CI 0.97-1.48) after adjusting for maternal age. A similar result was found for maternal age and risk of BPAD [HR 1.30 (95% CI 1.08-1.56) before adjustment for paternal age, HR 1.12 (95% Cl 0.86-1.45) after adjustment]. The HR associated with having either parent aged 30 years or over was 1.26 (95% CI 1.01-1.57) and it was 1.45 (95%, CI 1.16-1.81) if both parents were >30 years. Conclusions. Unlike schizophrenia, the risk of BPAD seems to be associated with both paternal and maternal ages.

Incidence of stroke subtypes, prognosis and prevalence of risk factors in Joinville, Brazil: a 2 year community based study

Background: There have been few population based studies on stroke risk factors and prognosis conducted in Brazil. The objective of this study was to evaluate, over a 2 year period, the incidence of the subtypes of first ever stroke, the prevalence of cardiovascular risk factors and functional prognosis in a city located in the south of Brazil. Methods: The period from January 2005 to December 2006 was evaluated prospectively by compiling data on first ever stroke cases, medications used prior to the morbidity and the incidence of traditional risk factors. The annual incidence was adjusted for age using the direct method. Patients were monitored for at least 6 months following the event. Results: Of 1323 stroke cases, 759 were first ever stroke cases. Of these, 610 were classified as infarctions, 94 as intracerebral haemorrhage and 55 as subarachnoid haemorrhage. The crude incidence rate per 100 000 inhabitants was 61.8 for infarction (95% CI 57.0 to 66.9), 9.5 for intracerebral haemorrhage (95% CI 7.7 to 11.6) and 5.6 for subarachnoid haemorrhage (95% CI 4.2 to 7.3). The 30 day case fatality was 19.1%. The most prevalent cardiovascular risk factor was arterial hypertension. By post-stroke month 6, 25% had died (95% CI 21.4 to 29.1) whereas 61.5% had regained their independence (95% CI 56.2 to 68.3). Conclusions: Case fatality rate, prognosis and incidence adjusted for stroke subtypes were similar to those found in other population based studies. The prevalence rates of ischaemic heart disease, dyslipidaemia, arterial hypertension and diabetes suggest that Joinville presents a mixed pattern of cardiovascular risk, a pattern seen in developed and developing countries alike.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

Because of the advent of a new influenza A H1N1. strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barre syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barre syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.