Should topical opioid analgesics be regarded as effective and safe when applied to chronic cutaneous lesions?

Objectives: The induction of analgesia for many chronic cutaneous lesions requires treatment with an opioid analgesic. In many patients suffering with these wounds such drugs are either contraindicated or shunned because of their association with death. There are now case reports involving over 100 patients with many different types of chronic superficial wounds, which suggest that the topical application of an opioid in a suitable gel leads to a significant reduction in the level of perceived pain. Key findings: Some work has been undertaken to elucidate the mechanisms by which such a reduction is achieved. To date there have been no proven deleterious effects of such an analgesic system upon wound healing. Although morphine is not absorbed through the intact epidermis, an open wound provides no such barrier and for large wounds drug absorption can be problematic. However, for most chronic cutaneous lesions, where data has been gathered, the blood levels of the drug applied ranges from undetectable to below that required for a systemic effect. Summary If proven, the use of opioids in this way would provide adequate analgesia for a collection of wounds, which are difficult to treat in patients who are often vulnerable. Proof of this concept is now urgently required. © 2011 Royal Pharmaceutical Society.

Análise da variabilidade da marcha de indivíduos com comprometimento articular unilateral do quadril por meio de sensores inerciais

Data variability analysis has been the focus of a number of studies seeking to capture differences of patterns generated by biological systems. Although several studies related to gait employ the analysis of variability in their observations, we noticed a lack of such information for subjects with unilateral coxarthrosis undergoing total hip arthroplasty (THA). To tackle this deficiency of information, we conducted a study of the gait on a treadmill with10 healthy subjects (30.7 ± 6.75 years old) from G1 and 24 subjects (65 ± 8.5 years old) with unilateral THA from G2. Thus, by means of two inertial measurement units (IMUs) positioned in the pelvis, we have developed a detection method of the step and stride for calculating these intervals and extract the signal characteristics. The variability analysis (coefficient of variation) was performed, taking into consideration the extracted features and the step and stride times. The average and the 95% confidence interval estimate for the average of the step and stride times to each group were in agreement with literature. The mean coefficient of variation for the step and stride times was calculated and compared among groups by the Kruskal-Wallis test with 95% confidence interval. Each component X, Y and Z of the two IMUs (accelerometer, magnetometer and gyroscope) corresponded to a variable. The resultants of each sensor, the linear velocity (accelerometers) and the instantaneous angular displacement (gyroscopes) completed the set of variables. The characteristics were extracted from the signals of these variables to check the variability in the G1 and G2 groups . There were significant differences (p <0.05) between G1 and G2 for the average of the step and stride times. The variability of the step and stride, as well as the variability of all other evaluated characteristics were higher for the group G2 (p <0.05). The method proposed in this study proved to be suitable for the measuring of variability of biomechanical parameters related to the extracted features. All the extracted features categorized the groups. The G2 group showed greater variability, so it is possible that the age and the pathological condition of the hip both contributed to this result.

Localising the auditory N1m with event-related beamformers:localisation accuracy following bilateral and unilateral stimulation

The auditory evoked N1m-P2m response complex presents a challenging case for MEG source-modelling, because symmetrical, phase-locked activity occurs in the hemispheres both contralateral and ipsilateral to stimulation. Beamformer methods, in particular, can be susceptible to localisation bias and spurious sources under these conditions. This study explored the accuracy and efficiency of event-related beamformer source models for auditory MEG data under typical experimental conditions: monaural and diotic stimulation; and whole-head beamformer analysis compared to a half-head analysis using only sensors from the hemisphere contralateral to stimulation. Event-related beamformer localisations were also compared with more traditional single-dipole models. At the group level, the event-related beamformer performed equally well as the single-dipole models in terms of accuracy for both the N1m and the P2m, and in terms of efficiency (number of successful source models) for the N1m. The results yielded by the half-head analysis did not differ significantly from those produced by the traditional whole-head analysis. Any localisation bias caused by the presence of correlated sources is minimal in the context of the inter-individual variability in source localisations. In conclusion, event-related beamformers provide a useful alternative to equivalent-current dipole models in localisation of auditory evoked responses.

Mitral Valve Surgery for Rheumatic Lesions in Young Patients

BACKGROUND: The appropriateness of rheumatic mitral valve repair remains controversial due to the risks of recurrent mitral dysfunction and need for reoperation. The aims of this study were to determine the overall short- and long-term outcomes of pediatric rheumatic mitral valve surgery in our center. METHODS: Single-center, observational, retrospective study that analyzed the results of rheumatic mitral valve surgery in young patients, consecutively operated by the same team, between 1999 and 2014. RESULTS: We included 116 patients (mean age = 12.6 ± 3.5 years), of which 66 (57%) were females. A total of 116 primary surgical interventions and 22 reoperations were performed. Primary valve repair was possible in 86 (74%) patients and valve replacement occurred in 30 (26%). Sixty percent of the patients were followed up beyond three months after surgery (median follow-up time = 9.2 months [minimum = 10 days; maximum = 15 years]). Long-term clinical outcomes were favorable, with most patients in New York Heart Association functional class I (89.6%) and in sinus rhythm (85%). Freedom from reoperation for primary valve repair at six months, five years, and ten years was 96.4% ± 0.25%, 72% ± 0.72%, and 44.7% ± 1.34%, respectively. Freedom from reoperation for primary valve replacement at six months, five years, and ten years was 100%, 91.7% ± 0.86%, and 91.7% ± 0.86%, respectively. Mitral stenosis as the primary lesion dictated early reintervention. CONCLUSIONS: Despite the greater rate of reoperation, especially when the primary lesion was mitral stenosis, rheumatic mitral valve repair provides similar clinical outcomes as compared with replacement, with the advantage of avoiding anticoagulation.

Proprioception in ankle sprain from exercises and bandages

Ankle sprains are the most common injuries in sports, usually causing damage to the lateral ligaments. Recurrence has as usual result permanent instability, and thus loss of proprioception. This fact, together with residual symptoms, is what is known as chronic ankle instability, CAI, or FAI, if it is functional. This problem tries to be solved by improving musculoskeletal stability and proprioception by the application of bandages and performing exercises. The aim of this study has been to review articles (meta-analisis, systematic reviews and revisions) published in 2009-2015 in PubMed, Medline, ENFISPO and BUCea, using keywords such as “sprain instability”, “sprain proprioception”, “chronic ankle instability”. Evidence affirms that there does exist decreased proprioception in patients who suffer from CAI. Rehabilitation exercise regimen is indicated as a treatment because it generates a subjective improvement reported by the patient, and the application of bandages works like a sprain prevention method limiting the range of motion, reducing joint instability and increasing confidence during exercise. As podiatrists we should recommend proprioception exercises to all athletes in a preventive way, and those with CAI or FAI, as a rehabilitation programme, together with the application of bandages. However, further studies should be generated focusing on ways of improving proprioception, and on the exercise patterns that provide the maximum benefit.

iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice.

Leishmania major parasites reside and multiply in late endosomal compartments of host phagocytic cells. Immune control of Leishmania growth absolutely requires expression of inducible Nitric Oxide Synthase (iNOS/NOS2) and subsequent production of NO. Here, we show that CD11b+ CD11c+ Ly-6C+ MHC-II+ cells are the main iNOS-producing cells in the footpad lesion and in the draining lymph node of Leishmania major-infected C57BL/6 mice. These cells are phenotypically similar to iNOS-producing inflammatory DC (iNOS-DC) observed in the mouse models of Listeria monocytogenes and Brucella melitensis infection. The use of DsRed-expressing parasites demonstrated that these iNOS-producing cells are the major infected population in the lesions and the draining lymph nodes. Analysis of various genetically deficient mouse strains revealed the requirement of CCR2 expression for the recruitment of iNOS-DC in the draining lymph nodes, whereas their activation is strongly dependent on CD40, IL-12, IFN-gamma and MyD88 molecules with a partial contribution of TNF-alpha and TLR9. In contrast, STAT-6 deficiency enhanced iNOS-DC recruitment and activation in susceptible BALB/c mice, demonstrating a key role for IL-4 and IL-13 as negative regulators. Taken together, our results suggest that iNOS-DC represent a major class of Th1-regulated effector cell population and constitute the most frequent infected cell type during chronic Leishmania major infection phase of C57BL/6 resistant mice.

Endoscopic band ligation without resection in selected patients for small and superficial upper gastrointestinal tract lesions

Background and aim: The aim of this study was to evaluate the efficacy of endoscopic band ligation (EBL) in carefully selected patients who would benefit from this method of resection. Methods: Patients with early upper gastrointestinal and small (< 15 mm) lesions treated with EBL (Duette® Multi-Band Mucosectomy) were prospectively recruited and retrospectively analyzed between 2010 and 2015. All cases were discussed in a multidisciplinary cancer committee and it was concluded that, owing to patient conditions, surgery was not possible and that not conducting histology would not change the clinical management. A first endoscopic control with biopsies was planned at 4-8 weeks. If there was no persistence of the lesion, new controls were programmed at 6 and 12 months. Results: The group (n = 12) included 5 esophagus lesions (adenosquamous carcinoma, n = 1; carcinoma squamous, n = 2; adenocarcinoma, n = 2); 4 gastric lesions (high grade dysplasia, n = 1; adenocarcinoma, n = 2; neuroendocrine tumor [NET], n = 1), and 3 duodenal lesions (NETs) (n = 3). The mean tumor diameter was 9.6 ± 2.8 mm (range 4-15). Only one minor adverse event was described. At first follow-up (4-8 weeks), there was 91.6% and 75% of endoscopic and histological remission, respectively. At 6-month follow-up there was 70% of both endoscopic remission and negative biopsies. And at 12 months, there was 100% and 75% of endoscopic and histological remission, respectively. Persisting lesions were T1 cancers. The median follow-up was 30.6 months. Conclusion: EBL without resection is an easy and safe technique that should be considered in patients with multiple morbidities and small superficial UGI lesions.

Clinical evaluation of two materials in the restoration of abfraction lesions

Aim: To evaluate the clinical performance of a composite resin (CR) and a resin-modified glassionomer cement (RMGIC) for the treatment of abfraction lesions. Methods: Thirty patients with abfraction lesions in at least two premolar teeth were selected and invited to participate in this study. All restorations were made within the same clinical time frame. One tooth was restored with CR Z100TM (3M, St. Paul, MN, USA), and the other was restored with RMGIC VitremerTM (3M). The restorations were assessed immediately and 1, 6 and 12 months after the restoration, using modified US Public Health Service (USPHS) criteria: marginal integrity, marginal discoloration, wear, retention, secondary caries and hypersensitivity. The statistical analysis was based on Friedman ANOVA test and Mann-Whitney test, considering p<0.05 for statistical significance. Results: Both materials demonstrated satisfactory clinical performance after one year. In the individual analysis of each material, there was a significant difference (p<0.05) in the criteria marginal integrity and wear, for both CR and RMGIC. RMGIC exhibited more damage one year after the restoration. Comparing both materials, it was found a significant difference only for marginal discoloration, while the RMGIC restorations showed the worst prognosis after a year of evaluation. There was no significant difference in the number of retentions, caries or hypersensitivity between CR and RMGIC. Conclusions: It was concluded that CR exhibited the best clinical performance according to the cost-effectiveness and evaluation criteria used in this study.

Uveítes felinas : etiologia e abordagem clínica

Dissertação de Mestrado Integrado em Medicina Veterinária

A cross-sectional survey of 5-year-old children with non-syndromic unilateral cleft lip and palate:the Cleft Care UK study. Part 1: background and methodology

OBJECTIVES: We describe the methodology for a major study investigating the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after an initial survey, detailed in the Clinical Standards Advisory Group (CSAG) report in 1998, had informed government recommendations on centralization. SETTING AND SAMPLE POPULATION: This is a UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Children born between 1 April 2005 and 31 March 2007 were seen in cleft centre audit clinics. MATERIALS AND METHODS: Consent was obtained for the collection of routine clinical measures (speech recordings, hearing, photographs, models, oral health, psychosocial factors) and anthropometric measures (height, weight, head circumference). The methodology for each clinical measure followed those of the earlier survey as closely as possible. RESULTS: We identified 359 eligible children and recruited 268 (74.7%) to the study. Eleven separate records for each child were collected at the audit clinics. In total, 2666 (90.4%) were collected from a potential 2948 records. The response rates for the self-reported questionnaires, completed at home, were 52.6% for the Health and Lifestyle Questionnaire and 52.2% for the Satisfaction with Service Questionnaire. CONCLUSIONS: Response rates and measures were similar to those achieved in the previous survey. There are practical, administrative and methodological challenges in repeating cross-sectional surveys 15 years apart and producing comparable data.

Centralization of cleft care in the UK. Part 6:a tale of two studies

OBJECTIVES: We summarize and critique the methodology and outcomes from a substantial study which has investigated the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after the UK government started to implement the centralization of cleft care in response to an earlier survey in 1998, the Clinical Standards Advisory Group (CSAG). SETTING AND SAMPLE POPULATION: A UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Data were collected from children born in the UK with a unilateral cleft lip and palate between 1 April 2005 and 31 March 2007. MATERIALS AND METHODS: We discuss and contextualize the outcomes from speech recordings, hearing, photographs, models, oral health and psychosocial factors in the current study. We refer to the earlier survey and other relevant studies. RESULTS: We present arguments for centralization of cleft care in healthcare systems, and we evidence this with improvements seen over a period of 15 years in the UK. We also make recommendations on how future audit and research may configure. CONCLUSIONS: Outcomes for children with a unilateral cleft lip and palate have improved after the introduction of a centralized multidisciplinary service, and other countries may benefit from this model. Predictors of early outcomes are still needed, and repeated cross-sectional studies, larger longitudinal studies and adequately powered trials are required to create a research-led evidence-based (centralized) service.

Antiangiogenic And Finasteride Therapies: Responses Of The Prostate Microenvironment In Elderly Mice.

The aim of this study was to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of senile mice. 90 male FVB mice were divided into: Young (18 weeks old) and senile (52 weeks old) groups; finasteride group: finasteride (20mg/kg); SU5416 group: SU5416 (6 mg/kg); TNP-470 group: TNP-470 (15 mg/kg,) and SU5416+TNP-470 group: similar to the SU5416 and TNP-470 groups. After 21 days, prostate ventral lobes were collected for morphological, immunohistochemical and Western blotting analyses. The results demonstrated atrophy, occasional proliferative lesions and inflammatory cells in the prostate during senescence, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. Decreased AR and endostatin reactivities, and an increase for ER-α, ER-β and VEGF, were seen in the senile group. Decreased VEGF and ER-α reactivities and increased ER-β reactivity were verified in the finasteride, SU5416 groups and especially in SU5416+TNP-470 group. The TNP-470 group showed reduced AR and ER-β protein levels. The senescence favored the occurrence of structural and/or molecular alterations suggesting the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. The SU5416+TNP-470 treatment was more effective in maintaining the structural, hormonal and angiogenic factor balance in the prostate during senescence, highlighting the signaling of antiproliferation via ER-β.

Advancing Bag-of-visual-words Representations For Lesion Classification In Retinal Images.

Diabetic Retinopathy (DR) is a complication of diabetes that can lead to blindness if not readily discovered. Automated screening algorithms have the potential to improve identification of patients who need further medical attention. However, the identification of lesions must be accurate to be useful for clinical application. The bag-of-visual-words (BoVW) algorithm employs a maximum-margin classifier in a flexible framework that is able to detect the most common DR-related lesions such as microaneurysms, cotton-wool spots and hard exudates. BoVW allows to bypass the need for pre- and post-processing of the retinographic images, as well as the need of specific ad hoc techniques for identification of each type of lesion. An extensive evaluation of the BoVW model, using three large retinograph datasets (DR1, DR2 and Messidor) with different resolution and collected by different healthcare personnel, was performed. The results demonstrate that the BoVW classification approach can identify different lesions within an image without having to utilize different algorithms for each lesion reducing processing time and providing a more flexible diagnostic system. Our BoVW scheme is based on sparse low-level feature detection with a Speeded-Up Robust Features (SURF) local descriptor, and mid-level features based on semi-soft coding with max pooling. The best BoVW representation for retinal image classification was an area under the receiver operating characteristic curve (AUC-ROC) of 97.8% (exudates) and 93.5% (red lesions), applying a cross-dataset validation protocol. To assess the accuracy for detecting cases that require referral within one year, the sparse extraction technique associated with semi-soft coding and max pooling obtained an AUC of 94.2 ± 2.0%, outperforming current methods. Those results indicate that, for retinal image classification tasks in clinical practice, BoVW is equal and, in some instances, surpasses results obtained using dense detection (widely believed to be the best choice in many vision problems) for the low-level descriptors.

Long-term Postoperative Atrophy Of Contralateral Hippocampus And Cognitive Function In Unilateral Refractory Mtle With Unilateral Hippocampal Sclerosis.

This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL). We performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals. The volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p<0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (± 2.5 SD; median=8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome. We observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms.

S-nitrosoglutathione (gsno) Is Cytotoxic To Intracellular Amastigotes And Promotes Healing Of Topically Treated Leishmania Major Or Leishmania Braziliensis Skin Lesions-authors' Response.

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