An in vitro study showing the three-dimensional microenvironment influence over the behavior of head and neck squamous cell carcinoma

Objectives: The Head and Neck Squamous Cell Carcinoma (HNSCC) ranks sixth worldwide. The mechanisms of growth, invasion and metastasis of this pathology are extensively studied and generally related to specific variations in signaling pathways like the PI3K-Akt; however most of these competent studies have been performed bidimensionally, which may hide important questions. This study sought to analyze the influence of the microenvironment upon the behavior of HNSCC. Study Design: The status of pAkt, NF-kappa B and Cyclin D1 proteins was accessed through immunofluorescence and western blot methods in HNSCC cell lines originating from tongue, pharynx and metastatic lymph node when submitted to a three-dimensional culture model utilizing a matrix system. A bidimensional culture model (monolayer) was used as control. Results: The HNSCC cell lines cultured three-dimensionally exhibited a growth pattern characterized by small isolated islands, different from the control group. When the three-dimensional model was applied, two of the studied cell lines showed the same expression pattern as the bidimensional model regarding nuclear or cytoplasmatic localization, as well as reduction of all protein levels; however, the cell line originated from tongue, which specially has the epidermal growth factor receptor constitutively activated, demonstrated nuclear translocation of pAkt and also an increase in the levels of Cyclin D1. Conclusions: The results suggest the influence of the microenvironment upon the behavior of HNSCC cells due to the changed expression of proteins related to tumor growth and cellular invasion. Furthermore, intrinsically genetic conditions also played important roles over the cells, despite the culture model employed.

Endoscopic Laser Thyroarytenoid Myoneurectomy in Patients with Adductor Spasmodic Dysphonia: A Pilot Study on Long-Term Outcome on Voice Quality

Objectives. Adductor spasmodic dysphonia (ADSD) is a focal laryngeal dystonia, which compromises greatly the quality of life of the patients involved. It is a severe vocal disorder characterized by spasms of laryngeal muscles during speech, producing phonatory breaks, forced, strained and strangled voice. Its symptoms result from involuntary and intermittent contractions of thyroarytenoid muscle during speech, which causes vocal fold to strain, pressing each vocal fold against the other and increasing glottic resistance. Botulinum toxin injection remains the gold-standard treatment. However, as injections should be repeated periodically leading to voice quality instability, a more definitive procedure would be desirable. In this pilot study we report the long-term vocal quality results of endoscopic laser thyroarytenoid myoneurectomy. Study Design. Prospective study. Methods. Surgery was performed in 15 patients (11 females and four males), aged between 29 and 73 years, diagnosed with ADSD. Voice Handicap Index (VHI) was obtained before and after surgery (median 31 months postoperatively). Results. A significant improvement in VHI was observed after surgery, as compared with baseline values (P = 0.001). The median and interquartile range for preoperative VHI was 99 and 13, respectively and 24 and 42, for postoperative VHI. Subjective improvement of voice as assessed by the patients showed median improvement of 80%. Conclusions. Because long-term follow-up showed significant improvement of voice quality, this innovative surgical technique seems a satisfactory alternative treatment of ADSD patients who seek a definite improvement of their condition.

Drospirenone and levonorgestrel in combination with either 30 or 20 mcg ethinylestradiol reduce soluble adhesion molecules in Brazilian women; cross-sectional study

Background: The objective of this study was to evaluate the effect of three contraceptive pills containing ethinylestradiol (EE) (20 or 30 mcg) in combination with drospirenone (DRSP) and levonorgestrel (LNG) on plasma concentration of adhesion molecules vascular cell adhesion molecule -1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Study Design: A cross-sectional study was conducted with 72 participants (18-30 years old) distributed into three groups that used oral contraceptives containing EE 20 or 30 mcg combined with DRSP 3 mg or EE 30 mcg/LNG 150 mcg for at least 6 months. The control group was comprised of nonusers of contraceptives. Soluble VCAM-1, soluble ICAM-1 and soluble E-selectin were evaluated by enzyme-linked immunosorbent assay. Results: Compared to the control group, a significant decrease was found in VCAM-1 and ICAM-1 concentrations with use of DRSP/20 EE and LNG/30 EE. Conclusions: DRSP/20 EE and LNG/30 EE induce favorable changes in endothelial function. (C) 2012 Elsevier Inc. All rights reserved.

Static postural balance study in patients with vestibular disorders using a three dimensional eletromagnetic sensor system

The vestibular-ocular reflex assessment is important, but not enough. Tridimensional electromagnetic sensor systems represent a new method to assess posturography. Aim: To assess body sway in healthy subjects who had positive Dix Hallpike and Epley maneuvers and with other vestibular dysfunctions by means of a three-dimensional system. Study design: Prospective. Materials and Methods: We had 23 healthy women, 15 with peripheral vestibular dysfunction found upon caloric test and 10 with positive Epley and Dix Hallpike maneuvers. All tests performed in the following positions: open and closed eyes on stable and unstable surfaces. Results: With the Eyes Open and on a stable surface, p < 0.01 between the control group and the one with peripheral vestibular dysfunction in all variables, except the a-p maximum, full speed and mediolateral trajectory velocity, which had a p < 0.01 between the group with vestibular dysfunction and controls in all positions. The group with positive Epley and Dix Hallpike maneuvers had p < 0.01 at full speed and in its components in the x and y in positions with open and eyes closed on an unstable surface. Conclusion: The tridimensional electromagnetic sensors system was able to generate reliable information about body sway in the study volunteers.

Software for subjective visual vertical assessment: an observational cross-sectional study

Spatial orientation in relation to the gravitational axis is significantly important for the maintenance of the posture, gait and for most of the human's motor activities. The subjective visual vertical exam evaluates the individual's perception of vertical orientation. Objectives: The aims of this study were (1) to develop a virtual system to evaluate the subjective visual vertical exam, (2) to provide a simple tool to clinical practice and (3) to assess the subjective visual vertical values of h ealthy subjects using the new software. Study Design: observational cross-sectional study. Methods: Thirty healthy volunteers performed the subjective visual vertical exam in both static and dynamic conditions. The exam consisted in adjusting a virtual line in the vertical position using the computer mouse. For the static condition, the virtual line was projected in a white background. For the dynamic condition, black circles rotated in clockwise or counterclockwise directions. Six measurements were taken and the mean deviations in relation to the real vertical calculated. Results: The mean values of subjective visual vertical measurements were: static -0.372 degrees; +/- 1.21; dynamic clockwise 1.53 degrees +/- 1.80 and dynamic counterclockwise -1.11 degrees +/- 2.46. Conclusion: This software showed to be practical and accurate to be used in clinical routines.

Food choices and practices during pregnancy of immigrant and Aboriginal women in Canada: a study protocol

Abstract Background Facilitating the provision of appropriate health care for immigrant and Aboriginal populations in Canada is critical for maximizing health potential and well-being. Numerous reports describe heightened risks of poor maternal and birth outcomes for immigrant and Aboriginal women. Many of these outcomes may relate to food consumption/practices and thus may be obviated through provision of resources which suit the women's ethnocultural preferences. This project aims to understand ethnocultural food and health practices of Aboriginal and immigrant women, and how these intersect with respect to the legacy of Aboriginal colonialism and to the social contexts of cultural adaptation and adjustment of immigrants. The findings will inform the development of visual tools for health promotion by practitioners. Methods/Design This four-phase study employs a case study design allowing for multiple means of data collection and different units of analysis. Phase 1 consists of a scoping review of the literature. Phases 2 and 3 incorporate pictorial representations of food choices (photovoice in Phase 2) with semi-structured photo-elicited interviews (in Phase 3). The findings from Phases 1-3 and consultations with key stakeholders will generate key understandings for Phase 4, the production of culturally appropriate visual tools. For the scoping review, an emerging methodological framework will be utilized in addition to systematic review guidelines. A research librarian will assist with the search strategy and retrieval of literature. For Phases 2 and 3, recruitment of 20-24 women will be facilitated by team member affiliations at perinatal clinics in one of the city's most diverse neighbourhoods. The interviews will reveal culturally normative practices surrounding maternal food choices and consumption, including how women negotiate these practices within their own worldview and experiences. A structured and comprehensive integrated knowledge translation plan has been formulated. Discussion The findings of this study will provide practitioners with an understanding of the cultural differences that affect women's dietary choices during maternity. We expect that the developed resources will be of immediate use within the women's units and will enhance counseling efforts. Wide dissemination of outputs may have a greater long term impact in the primary and secondary prevention of these high risk conditions.

Biomarkers and Bacterial Pneumonia Risk in Patients with Treated HIV Infection: A Case-Control Study

Background: Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIVinfected patients do not currently exist. Methods: We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1:1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls. Results: Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm3. Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 mg/mL in cases vs. 1.93 mg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively). Conclusions: In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.

Risk factors associated with death in Brazilian children with severe dengue: a case-control study

Objective: The purpose of this case-control study was to evaluate risk factors associated with death in children with severe dengue. Methods: The clinical condition of hospitalized patients with severe dengue who died (cases, n = 18) was compared with that of hospitalized patients with severe dengue who survived (controls, n = 77). The inclusion criteria for this study were age under 13 years; hospital admission in São Luis, northeastern Brazil; and laboratory-confirmed diagnosis of dengue. Results: Severe bleeding (hemoptysis), a defining criterion for dengue severity, was the factor most strongly associated with death in our study. We also found that epistaxis and persistent vomiting, both included as warning signs in the World Health Organization (WHO) classification of dengue, were strongly associated with death. No significant association was observed between any of the laboratory findings and death. Conclusions: The finding that epistaxis and persistent vomiting were also associated with death in children with severe dengue was unexpected and deserves to be explored in future studies. Because intensive care units are often limited in resource-poor settings, any information that can help to distinguish patients with severe dengue with a higher risk to progress to death may be crucial.

Microfenestration using the CUSA Excel ultrasonic aspiration system in chondrodystrophic dogs with thoracolumbar disk extrusion: a descriptive cadaveric and clinical study

OBJECTIVE: To describe an ultrasonic surgical aspirator assisted disk fenestration technique in dogs. STUDY DESIGN: Descriptive cadaveric and prospective clinical study. ANIMALS: Fresh Beagle cadavers (n=5) and 10 chondrodystrophic dogs with thoracolumbar disk extrusion. METHODS: Cadaveric study: Intervertebral disks T12-L2 were fenestrated with the CUSA Excel in 5 Beagle cadavers, and fenestration efficacy assessed by morphologic examination of the completeness of fenestration and size of annulotomy. Clinical study: the affected intervertebral disk was fenestrated in 10 chondrodystrophic dogs treated by hemilaminectomy for thoracolumbar disk disease. Efficacy of fenestration was evaluated. RESULTS: Mean time necessary to perform CUSA assisted fenestration was 8 minutes (range, 5-10 minutes) for each disk in cadavers and patients. In cadaver spines, removal of the nucleus pulposus was complete in 11/15 disks. In 4 disks, remnants of nucleus pulposus material were observed on the contralateral side. Nuclear material was normal in 9/15 disks and showed evidence of chondroid degeneration on histopathologic examination in the 6 disks. Median annulotomy size was 3 mm. Clinically, no signs of early recurrence were observed and all dogs recovered uneventfully. CONCLUSIONS: CUSA assisted fenestration is a safe and efficient method of fenestration for removal of most of the nucleus pulposus through a limited annulotomy.

Influence of Partial Lateral Corpectomy with and without Hemilaminectomy on Canine Thoracolumbar Stability: A Biomechanical Study

OBJECTIVE: To analyze the biomechanical changes induced by partial lateral corpectomy (PLC) and a combination of PLC and hemilaminectomy in a T13-L3 spinal segment in nonchondrodystrophic dogs. STUDY DESIGN: In vitro biomechanical cadaveric study. SAMPLE POPULATION: T13-L3 spinal segments (n = 10) of nonchondrodystrophic dogs (weighing, 25-38 kg). METHODS: A computed tomography (CT) scan of each T13-L3 spinal segment was performed. A loading simulator for flexibility analysis was used to determine the range of motion (ROM) and neutral zone (NZ) during flexion/extension, lateral bending, and axial rotation. A servohydraulic testing machine was used to determine the changes in stiffness during compression, dorsoventral, and lateral shear. All spines were tested intact, after PLC in the left intervertebral space of L1-L2, and after a combination of PLC and hemilaminectomy. RESULTS: Statistically significant increases in ROM and NZ (P < .05) were detected during flexion/extension and lateral bending when PLC was performed. A significant increase in ROM (P < .001) was noted during axial rotation and flexion after PLC and hemilaminectomy. Stiffness decreased significantly during compression and dorsoventral shear after each procedure. Decreased stiffness during lateral shear was only significant after a combination of both procedures. CONCLUSION: PLC might lead to some spinal instability; these changes are enhanced when a hemilaminectomy is added.

Incidence of spinal compressive lesions in chondrodystrophic dogs with abnormal recovery after hemilaminectomy for treatment of thoracolumbar disc disease: a prospective magnetic resonance imaging study

OBJECTIVE: To investigate causes of the lack of clinical improvement after thoracolumbar disc surgery. STUDY DESIGN: Case-control magnetic resonance imaging (MRI) study. ANIMALS: Chondrodystrophic dogs with acute thoracolumbar disc disease treated by hemilaminectomy: 10 that had no short-term clinical improvement and 12 with "normal" clinical improvement. METHODS: Dogs that had surgery for treatment of intervertebral disc extrusion (2003-2008) where thoracolumbar disc disease was confirmed by MRI were evaluated to identify dogs that had lack of clinical improvement after surgery. Ten dogs with delayed recovery or clinical deterioration were reexamined with MRI and compared with 12 dogs with normal recovery and MRI reexamination after 6 weeks (control group). RESULTS: Of 173 dogs, 10 (5.8%) had clinical deterioration within 1-10 days after surgery. In 8 dogs, residual spinal cord compression was identified on MRI. Bleeding was present in 1 dog. In 3 dogs, the cause was an incorrect approach and insufficient disc material removal. In 3 dogs, recurrence occurred at the surgical site. In 1 dog, the centrally located extruded material was shifted to the contralateral side during surgery. These 8 dogs had repeat surgery and recovery was uneventful. In 2 dogs, deterioration could not be associated with a compressive disc lesion. Hemorrhagic myelomalacia was confirmed by pathologic examination in 1 dog. The other dog recovered after 6 months of conservative management. CONCLUSION: Delayed postsurgical recovery or deterioration is commonly associated with newly developed and/or remaining compressive disc lesion. CLINICAL RELEVANCE: We recommend early MRI reexamination to assess the postsurgical spinal canal and cord, and to plan further therapeutic measures in chondrodystrophic dogs with delayed recovery after decompressive hemilaminectomy for thoracolumbar disc disease.

Ultrasound-guided retrobulbar nerve block in horses: a cadaveric study

Objective  To develop an ultrasound-guided technique for retrobulbar nerve block in horses, and to compare the distribution of three different volumes of injected contrast medium (CM) (4, 8 and 12 mL), with the hypothesis that successful placement of the needle within the retractor bulbi muscle cone would lead to the most effective dispersal of CM towards the nerves leaving the orbital fissure. Study design  Prospective experimental cadaver study. Animals  Twenty equine cadavers. Methods  Ultrasound-guided retrobulbar injections were performed in 40 cadaver orbits. Ultrasound visualization of needle placement within the retractor bulbi muscle cone and spread of injected CM towards the orbital fissure were scored. Needle position and destination of CM were then assessed using computerized tomography (CT), and comparisons performed between ultrasonographic visualization of orbital structures and success rate of injections (intraconal needle placement, CM reaching the orbital fissure). Results  Higher scores for ultrasound visualization resulted in a higher success rate for intraconal CM injection, as documented on the CT images. Successful intraconal placement of the needle (22/34 orbits) resulted in CM always reaching the orbital fissure. CM also reached the orbital fissure in six orbits where needle placement was extraconal. With 4, 8 and 12 mL CM, the orbital fissure was reached in 16/34, 23/34 and 28/34 injections, respectively. Conclusion and clinical relevance  The present study demonstrates the use of ultrasound for visualization of anatomical structures and needle placement during retrobulbar injections in equine orbits. However, this approach needs to be repeated in controlled clinical trials to assess practicability and effectiveness in clinical practice.

The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study

BACKGROUND: IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma. OBJECTIVE: To examine the relationship of a genetic, haplotype-tagging promotor variant -137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults. METHODS: Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy. RESULTS: The G-allele of the IL-18 promotor variant (-137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 -137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64-8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66-1.94). The interaction between IL-18 -137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. CONCLUSION: Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma.

Acute stress reactions in the first 3 weeks postpartum: A study of 219 parturients

OBJECTIVES: There is increasing research on posttraumatic stress (PS) 4-6 weeks and 3 months postpartum, but, there are no data on acute stress reactions (ASR) in the first 3 weeks postpartum, i.e. the potential precursors of PS. However, ASR may have long-term effects, e.g., on a subsequent pregnancy without having manifested as PS in the meantime. We propose: (i) to describe the patterns of ASR after childbirth, (ii) to explore differences between women with normal and traumatogenic ASR, and (iii) to provide data on the early detection of traumatogenic ASR 2 and 3 weeks postpartum. STUDY DESIGN: Intra-event variables (relationship with caregivers, overall birth experience, and dissociative experiences, as well as obstetric variables) were assessed 48-96h. postpartum, as were ASR (by means of the Impact-of-Event Scale IES) in weeks 1, 2, and 3 postpartum. According to research on PS the upper 33%-range of ASR in weeks 2 and 3 was defined as 'traumatogenic'. RESULTS: Normal ASR in week 1 are at a level which in non-obstetric trauma-situations is considered as the upper range of low stress or lower range of medium distress. ASR decline constantly from week 1 to week 3. However, high ASR in week 1 do not drop faster than do low ones, thus indicating a prolonged stress reaction in women with high ASR in week 1. Low ASR (IES-scores <10) and high ASR (IES-scores >20) in week 1 are highly predictive for normal ASR, and traumatogenic ASR in weeks 2 and 3, respectively. Medium ASR (IES-scores 10-20) in week 1 are of uncertain predictive value for stress reactions in weeks 2 and 3 and have to be re-assessed at that time. CONCLUSIONS: Clinical screening for ASR appears to be helpful in detecting women with a compromised ability to process childbirth-related stress. The association between ASR and long-term development should be further explored.

Internet based multicenter study for thoracolumbar injuries: a new concept and preliminary results

This article reports about the internet based, second multicenter study (MCS II) of the spine study group (AG WS) of the German trauma association (DGU). It represents a continuation of the first study conducted between the years 1994 and 1996 (MCS I). For the purpose of one common, centralised data capture methodology, a newly developed internet-based data collection system ( http://www.memdoc.org ) of the Institute for Evaluative Research in Orthopaedic Surgery of the University of Bern was used. The aim of this first publication on the MCS II was to describe in detail the new method of data collection and the structure of the developed data base system, via internet. The goal of the study was the assessment of the current state of treatment for fresh traumatic injuries of the thoracolumbar spine in the German speaking part of Europe. For that reason, we intended to collect large number of cases and representative, valid information about the radiographic, clinical and subjective treatment outcomes. Thanks to the new study design of MCS II, not only the common surgical treatment concepts, but also the new and constantly broadening spectrum of spine surgery, i.e. vertebro-/kyphoplasty, computer assisted surgery and navigation, minimal-invasive, and endoscopic techniques, documented and evaluated. We present a first statistical overview and preliminary analysis of 18 centers from Germany and Austria that participated in MCS II. A real time data capture at source was made possible by the constant availability of the data collection system via internet access. Following the principle of an application service provider, software, questionnaires and validation routines are located on a central server, which is accessed from the periphery (hospitals) by means of standard Internet browsers. By that, costly and time consuming software installation and maintenance of local data repositories are avoided and, more importantly, cumbersome migration of data into one integrated database becomes obsolete. Finally, this set-up also replaces traditional systems wherein paper questionnaires were mailed to the central study office and entered by hand whereby incomplete or incorrect forms always represent a resource consuming problem and source of error. With the new study concept and the expanded inclusion criteria of MCS II 1, 251 case histories with admission and surgical data were collected. This remarkable number of interventions documented during 24 months represents an increase of 183% compared to the previously conducted MCS I. The concept and technical feasibility of the MEMdoc data collection system was proven, as the participants of the MCS II succeeded in collecting data ever published on the largest series of patients with spinal injuries treated within a 2 year period.