Optic Disc Margin Anatomy in Patients with Glaucoma and Normal Controls with Spectral Domain Optical Coherence Tomography

Objective: To characterize optic nerve head (ONH) anatomy related to the clinical optic disc margin with spectral domain-optical coherence tomography (SD-OCT). Design: Cross-sectional study. Participants: Patients with open-angle glaucoma with focal, diffuse, and sclerotic optic disc damage, and age-matched normal controls. Methods: High-resolution radial SD-OCT B-scans centered on the ONH were analyzed at each clock hour. For each scan, the border tissue of Elschnig was classified for obliqueness (internally oblique, externally oblique, or nonoblique) and the presence of Bruch's membrane overhanging the border tissue. Optic disc stereophotographs were co-localized to SD-OCT data with customized software. The frequency with which the disc margin identified in stereophotographs coincided with (1) Bruch's membrane opening (BMO), defined as the innermost edge of Bruch's membrane; (2) Bruch's membrane/border tissue, defined as any aspect of either outside BMO or border tissue; or (3) border tissue, defined as any aspect of border tissue alone, in the B-scans was computed at each clock hour. Main Outcome Measures: The SD-OCT structures coinciding with the disc margin in stereophotographs. Results: There were 30 patients (10 with each type of disc damage) and 10 controls, with a median (range) age of 68.1 (42-86) years and 63.5 (42-77) years, respectively. Although 28 patients (93%) had 2 or more border tissue configurations, the most predominant one was internally oblique, primarily superiorly and nasally, frequently with Bruch's membrane overhang. Externally oblique border tissue was less frequent, observed mostly inferiorly and temporally. In controls, there was predominantly internally oblique configuration around the disc. Although the configurations were not statistically different between patients and controls, they were among the 3 glaucoma groups. At most locations, the SD-OCT structure most frequently identified as the disc margin was some aspect of Bruch's membrane and border tissue external to BMO. Bruch's membrane overhang was regionally present in the majority of patients with glaucoma and controls; however, in most cases it was not visible as the disc margin. Conclusions: The clinically perceived disc margin is most likely not the innermost edge of Bruch's membrane detected by SD-OCT. These findings have important implications for the automated detection of the disc margin and estimates of the neuroretinal rim. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:738-747 (C) 2012 by the American Academy of Ophthalmology.

Rates of Change in the Visual Field and Optic Disc in Patients with Distinct Patterns of Glaucomatous Optic Disc Damage

Purpose: To investigate the rate of visual field and optic disc change in patients with distinct patterns of glaucomatous optic disc damage. Design: Prospective longitudinal study. Participants: A total of 131 patients with open-angle glaucoma with focal (n = 45), diffuse (n = 42), and sclerotic (n = 44) optic disc damage. Methods: Patients were examined every 4 months with standard automated perimetry (SAP, SITA Standard, 24-2 test, Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA) and confocal scanning laser tomography (CSLT, Heidelberg Retina Tomograph, Heidelberg Engineering GmbH, Heidelberg, Germany) for a period of 4 years. During this time, patients were treated according to a predefined protocol to achieve a target intraocular pressure (IOP). Rates of change were estimated by robust linear regression of visual field mean deviation (MD) and global optic disc neuroretinal rim area with follow-up time. Main Outcome Measures: Rates of change in MD and rim area. Results: Rates of visual field change in patients with focal optic disc damage (mean -0.34, standard deviation [SD] 0.69 dB/year) were faster than in patients with sclerotic (mean - 0.14, SD 0.77 dB/year) and diffuse (mean + 0.01, SD 0.37 dB/year) optic disc damage (P = 0.003, Kruskal-Wallis). Rates of optic disc change in patients with focal optic disc damage (mean - 11.70, SD 25.5 x 10(-3) mm(2)/year) were faster than in patients with diffuse (mean -9.16, SD 14.9 x 10(-3) mm(2)/year) and sclerotic (mean -0.45, SD 20.6 x 10(-3) mm(2)/year) optic disc damage, although the differences were not statistically significant (P = 0.11). Absolute IOP reduction from untreated levels was similar among the groups (P = 0.59). Conclusions: Patients with focal optic disc damage had faster rates of visual field change and a tendency toward faster rates of optic disc deterioration when compared with patients with diffuse and sclerotic optic disc damage, despite similar IOP reductions during follow-up. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012; 119: 294-303 (C) 2012 by the American Academy of Ophthalmology.

Toll-like receptor 2 knockdown modulates Interleukin (IL)-6 and IL-8 but not Stromal Derived Factor-1 (SDF-1/CXCL12) in human periodontal ligament and gingival fibroblasts

Background: Fibroblasts are now seen as active components of the immune response because these cells express Toll-like receptors (TLRs), recognize pathogen-associated molecular patterns, and mediate the production of cytokines and chemokines during inflammation. The innate host response to lipopolysaccharide (LPS) from Porphyromonas gingivalis is unusual inasmuch as different studies have reported that it can be an agonist for Toll-like receptor 2 (TLR2) and an antagonist or agonist for Toll-like receptor 4 (TLR4). This study investigates and compares whether signaling through TLR2 or TLR4 could affect the secretion of interleukin (IL)-6, IL-8, and stromal derived factor-1 (SDF-1/CXCL12) in both human gingival fibroblasts (HGF) and human periodontal ligament fibroblasts (HPDLF). Methods: After small interfering RNA-mediated silencing of TLR2 and TLR4, HGF and HPDLF from the same donors were stimulated with P. gingivalis LPS or with two synthetic ligands of TLR2, Pam2CSK4 and Pam3CSK4, for 6 hours. IL-6, IL-8, and CXCL12 mRNA expression and protein secretion were evaluated by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Results: TLR2 mRNA expression was upregulated in HGF but not in HPDLF by all the stimuli applied. Knockdown of TLR2 decreased IL-6 and IL-8 in response to P. gingivalis LPS, or Pam2CSK4 and Pam3CSK4, in a similar manner in both fibroblasts subpopulations. Conversely, CXCL12 remained unchanged by TLR2 or TLR4 silencing. Conclusion: These results suggest that signaling through TLR2 by gingival and periodontal ligament fibroblasts can control the secretion of IL-6 and IL-8, which contribute to periodontal pathogenesis, but do not interfere with CXCL12 levels, an important chemokine in the repair process.

Treatment of snoring and sleep apnea syndrome with a removable mandibular advancement device in patients without TMD

INTRODUCTION: Among the sleep disorders reported by the American Academy of Sleep, the most common is obstructive sleep apnea-hypopnea syndrome (OSAHS), which is caused by difficulties in air passage and complete interruption of air flow in the airway. This syndrome is associated with increased morbidity and mortality in apneic individuals. OBJECTIVE: It was the objective of this paper to evaluate a removable mandibular advancement device as it provides a noninvasive, straightforward treatment readily accepted by patients. METHODS: In this study, 15 patients without temporomandibular disorders (TMD) and with excessive daytime sleepiness or snoring were evaluated. Data were collected by means of: Polysomnography before and after placement of an intraoral appliance, analysis of TMD signs and symptoms using a patient history questionnaire, muscle and TMJ palpation. RESULTS: After treatment, the statistical analysis (t-test, and the "before and after" test) showed a mean reduction of 77.6% (p=0.001) in the apnea-hypopnea index, an increase in lowest oxyhemoglobin saturation (p=0.05), decrease in desaturation (p=0.05), decrease in micro-awakenings or EEG arousals (p=0.05) and highly significant improvement in daytime sleepiness (p=0.005), measured by the Epworth Sleepiness Scale. No TMD appeared during the monitoring period. CONCLUSION: The oral device developed in this study was considered effective for mild to moderate OSAHS.

Survey of Trachoma within School Students in the State of Roraima, Brazil

Purpose: Trachoma, a blinding conjunctivitis, is the result of repeated infection with Chlamydia trachomatis. There are no recent data for the state of Roraima, Brazil, where it was thought that trachoma no longer existed. These data are derived from school children sampled in this state, with additional data collected from the contacts of children with trachoma. Design: A population-based cross-sectional study with random sampling of students in grades 1 through 4 of all public schools within municipalities where the human development index was less than the national average in 2003. The sample was stratified according to population size. Participants: A sample size of 7200 was determined and a total of 6986 (93%) students were examined, along with an additional 2152 contacts. Methods: All students were examined for trachoma according to World Health Organization criteria. Demographic data and contact information also was collected. The family and school contacts of students with trachoma then were located and examined. Main Outcome Measures: Prevalence and grade of trachoma, age, gender, race, and municipality location. Results: The overall prevalence of trachoma was 4.5% (95% confidence interval [CI], 3.7%–5.3%), but there were municipalities within the state where the prevalence of inflammatory trachoma was more than 10%. The prevalence was greater in rural areas (4.9%; 95% CI, 3.7%–6.0%) compared with urban areas (3.9%; 95% CI, 2.9%–4.9%). Living in indigenous communities was associated with trachoma (odds ratio, 1.6; 95% CI, 0.9 –2.6). An additional 2152 contacts were examined, and the overall trachoma prevalence was 9.3% (95% CI, 8.1–10.5). Conclusions: Trachoma continues to exist in Roraima, Brazil, where there are municipalities with a significant prevalence of disease. The indigenous population is highly mobile, crossing state and international borders, raising the possibility of trachoma in neighboring countries. Trachoma prevalence among the contacts of students with trachoma was higher than the school population, highlighting the importance of contact tracing.

Analysis of cerebral and autonomic response to respiratory events in patients with Sleep Apnea Syndrome

The arousal scoring in Obstructive Sleep Apnea Syndrome (OSAS) is important to clarify the impact of the disease on sleep but the currently applied American Academy of Sleep Medicine (AASM) definition may underestimate the subtle alterations of sleep. The aims of the present study were to evaluate the impact of respiratory events on cortical and autonomic arousal response and to quantify the additional value of cyclic alternating pattern (CAP) and pulse wave amplitude (PWA) for a more accurate detection of respiratory events and sleep alterations in OSAS patients. A retrospective revision of 19 polysomnographic recordings of OSAS patients was carried out. Analysis was focused on quantification of apneas (AP), hypopneas (H) and flow limitation (FL) events, and on investigation of cerebral and autonomic activity. Only 41.1% of FL events analyzed in non rapid eye movement met the AASM rules for the definition of respiratory event-related arousal (RERA), while 75.5% of FL events ended with a CAP A phase. The dual response (EEG-PWA) was the most frequent response for all subtypes of respiratory event with a progressive reduction from AP to H and FL. 87.7% of respiratory events with EEG activation showed also a PWA drop and 53,4% of the respiratory events without EEG activation presented a PWA drop. The relationship between the respiratory events and the arousal response is more complex than that suggested by the international classification. In the estimation of the response to respiratory events, the CAP scoring and PWA analysis can offer more extensive information compared to the AASM rules. Our data confirm also that the application of PWA scoring improves the detection of respiratory events and could reduce the underestimation of OSAS severity compared to AASM arousal.

High numbers of DC-SIGN+ dendritic cells in lesional skin of cutaneous T-cell lymphoma

The role of dendritic cells (DCs) in disease progression of primary cutaneous T-cell lymphoma (CTCL) is not well understood. With their unique ability to induce primary immune responses as well as immunotolerance, DCs play a critical role in mediation of anti-tumor immune responses. Tumor-infiltrating DCs have been determined to represent important prognostic factors in a variety of human tumors.

Early loading at 21 days of non-submerged titanium implants with a chemically modified sandblasted and acid-etched surface: 3-year results of a prospective study in the posterior mandible

BACKGROUND: This study evaluates 3-year success rates of titanium screw-type implants with a chemically modified sandblasted and acid-etched surface (mod SLA), which were functionally loaded after 3 weeks of healing. METHODS: A total of 56 implants, inserted in the posterior mandibles of 39 partially edentulous patients, underwent undisturbed healing for 3 weeks. At day 21, the implants were fully loaded with provisional crowns. Definitive metal ceramic restorations were fabricated after 6 months of healing. Clinical measurements regarding soft tissue parameters and radiographs were obtained at different time points up to 36 months after implant placement. The soft tissue and radiographic parameters for the mod SLA implants after 3 years in function were compared to a historic control group of implants with an SLA surface using an early loading protocol after 6 weeks. RESULTS: None of the implants failed to integrate. However, two implants were considered "spinners" at day 21 and were left unloaded for an extended period. Therefore, 96.4% of the inserted implants were loaded according to the protocol tested. All 56 implants, including the "spinners," showed favorable clinical and radiographic findings at the 3-year follow-up examination. All 56 implants were considered successfully integrated, resulting in a 3-year survival and success rate of 100%. Dental implants with a mod SLA surface demonstrated statistically significant differences for probing depths and clinical attachment level values compared to the historic control group, with the mod SLA surface implants having overall lower probing depths and clinical attachment level scores. CONCLUSION: This prospective study using an early loading protocol demonstrates that titanium implants with the mod SLA surface can achieve and maintain successful tissue integration over a period of 3 years.

Stability of Contour Augmentation and Esthetic Outcomes of Implant Supported Single Crowns in the Esthetic Zone. 3-Year Results of a Prospective Study With Early Implant Placement Post Extraction

Early implant placement is one of the treatment options after tooth extraction. Implant surgery is performed after a healing period of 4 to 8 weeks and combined with a simultaneous contour augmentation using the guided bone regeneration technique to rebuild stable esthetic facial hard- and soft-tissue contours.

Clinical and Histological Evaluation of a Granular Bovine Bone Biomaterial Used as an Adjunct to Guided Tissue Regeneration With a Bioresorbable Bovine Pericardium Collagen Membrane in the Treatment of Intrabony Periodontal Defects

The aim of the present study is to evaluate the clinical and histologic healing of deep intrabony defects treated with guided tissue regeneration (GTR) with a collagen membrane from bovine pericardium and implantation of granular bovine bone biomaterial.

Day/Night rhythm of hemostatic factors in obstructive sleep apnea

To investigate the hypothesis that day/night patterns of prothrombotic activity differ between patients with obstructive sleep apnea (OSA) and individuals with no OSA.

Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review

BACKGROUND: Worldwide, diarrheal diseases rank second among conditions that afflict children. Despite the disease burden, there is limited consensus on how to define and measure pediatric acute diarrhea in trials. OBJECTIVES: In RCTs of children involving acute diarrhea as the primary outcome, we documented (1) how acute diarrhea and its resolution were defined, (2) all primary outcomes, (3) the psychometric properties of instruments used to measure acute diarrhea and (4) the methodologic quality of included trials, as reported. METHODS: We searched CENTRAL, Embase, Global Health, and Medline from inception to February 2009. English-language RCTs of children younger than 19 years that measured acute diarrhea as a primary outcome were chosen. RESULTS: We identified 138 RCTs reporting on 1 or more primary outcomes related to pediatric acute diarrhea/diseases. Included trials used 64 unique definitions of diarrhea, 69 unique definitions of diarrhea resolution, and 46 unique primary outcomes. The majority of included trials evaluated short-term clinical disease activity (incidence and duration of diarrhea), laboratory outcomes, or a composite of these end points. Thirty-two trials used instruments (eg, single and multidomain scoring systems) to support assessment of disease activity. Of these, 3 trials stated that their instrument was valid; however, none of the trials (or their citations) reported evidence of this validity. The overall methodologic quality of included trials was good. CONCLUSIONS: Even in what would be considered methodologically sound clinical trials, definitions of diarrhea, primary outcomes, and instruments employed in RCTs of pediatric acute diarrhea are heterogeneous, lack evidence of validity, and focus on indices that may not be important to participants.

Fatal pulmonary embolism in a premature neonate after twin-to-twin transfusion syndrome

Thrombotic events are being increasingly recognized during the neonatal period. An infant girl was born at 29 weeks' gestation after a pregnancy complicated by twin-to-twin transfusion syndrome. After an initial uncomplicated clinical course, her oxygen requirement increased, which was interpreted as an early sign of bronchopulmonary dysplasia. At 3 weeks of age, she suddenly collapsed and died of severe pulmonary hypertension. At autopsy, multiple pulmonary artery emboli and several older renal vein thromboses were found. Results of genetic analyses of the infant and her family were negative for thrombophilia. Although embolism represents a frequent emergency in adults, fatal pulmonary embolism has never, to our knowledge, been described for premature infants. This case suggests that thrombotic events are underdiagnosed and that additional studies are needed to define infants at risk and optimal treatment strategies.

Periosteal Distraction Osteogenesis and Barrier Membrane Application: An Experimental Study in the Rat Calvaria

Background: Distraction of the periosteum results in the formation of new bone in the gap between the periosteum and the original bone. We postulate that the use of a barrier membrane would be beneficial for new bone formation in periosteal distraction. Methods: To selectively influence the contribution of the periosteum, a distraction plate with perforations was used alone or covered by a collagen barrier membrane. All animals were subjected to a 7-day latency period and a 10-day distraction period with a rate of 0.1 mm/day. Four animals per group with or without a barrier membrane were sacrificed at 2, 4, and 6 weeks after the end of the distraction. The height of new bone generated relative to the areas bound by the parent bone and the periosteum was determined by histomorphometric methods. Results: New bone was found in all groups. At the periphery of the distraction plate, significant differences in bone height were found between the hinge and the distraction screw for the group without barrier membrane at 2 weeks (0.39 ± 0.19 mm) compared to 4 weeks (0.84 ± 0.44 mm; P = 0.002) and 6 weeks (1.06 ± 0.39 mm; P = 0.004). Differences in maximum bone height with and without a barrier membrane were observed laterally to the distraction plate at 2 weeks (1.22 ± 0.64 versus 0.55 ± 0.14 mm; P = 0.019) and 6 weeks (1.61 ± 0.56 versus 0.73 ± 0.33 mm; P = 0.003) of the consolidation period. Conclusion: Within the limitations of the present study, the application of a barrier membrane may be considered beneficial for new bone formation induced by periosteal distraction.

Effect of enamel matrix derivative and parathyroid hormone on bone formation in standardized osseous defects: an experimental study in minipigs

Previous experimental studies have indicated that locally administered enamel matrix derivative (EMD) and parathyroid hormone (PTH) may have a stimulatory effect on bone formation. However, it is not clear if the positive effect of EMD is related to its effect on the periodontium as a whole or directly on the bone-forming cells. In addition, it is not known if the presentation of PTH by adding the amino acid sequence Arg-Gly-Asp (RGD) is essential for its osteopromotive effect. Local delivery of a bioactive substance at the right time and in the right concentration often constitutes a major challenge. Polyethylene glycol-based hydrogel (PEG) is a degradable vehicle developed for delivery of bioactive proteins. To enhance the mechanical stability of the PEG-bioactive substance complex, an osteoconductive bone substitute material is often needed.