A survey in the West Midlands of the United Kingdom of current practice in managing hypotension in lower segment caesarean section under spinal anaesthesia.

BACKGROUND: Spinal anaesthesia, the most common form of anaesthesia for caesarean section, leads to sympathetic blockade and profound maternal hypotension resulting in adverse maternal and neonatal outcomes. Hypotension, nausea and vomiting remain common but until the publication of the National Institute of Health and Care Excellence (NICE) 2021 guidance, no national guideline existed on how best to manage maternal hypotension following spinal anaesthesia for caesarean section. A 2017 international consensus statement recommended prophylactic vasopressor administration to maintain a systolic blood pressure of >90% of an accurate pre-spinal value, and to avoid a drop to <80% of this value. This survey aimed to assess regional adherence to these recommendations, the presence of local guidelines for management of hypotension during caesarean section under spinal anaesthesia, and the individual clinician's treatment thresholds for maternal hypotension and tachycardia. METHODS: The West Midlands Trainee-led Research in Anaesthesia and Intensive Care Network co-ordinated surveys of obstetric anaesthetic departments and consultant obstetric anaesthetists across 11 National Health Service Trusts in the Midlands, England. RESULTS: One-hundred-and-two consultant obstetric anaesthetists returned the survey and 73% of sites had a policy for vasopressor use; 91% used phenylephrine as the first-line drug but a wide range of recommended delivery methods was noted and target blood pressure was only listed in 50% of policies. Significant variation existed in both vasopressor delivery methods and target blood pressures. CONCLUSIONS: Although NICE has since recommended prophylactic phenylephrine infusion and a target blood pressure, the previous international consensus statement was not adhered to routinely.

Osteoimmune regulation underlies oral implant osseointegration and its perturbation.

In the field of biomaterials, an endosseous implant is now recognized as an osteoimmunomodulatory but not bioinert biomaterial. Scientific advances in bone cell biology and in immunology have revealed a close relationship between the bone and immune systems resulting in a field of science called osteoimmunology. These discoveries have allowed for a novel interpretation of osseointegration as representing an osteoimmune reaction rather than a classic bone healing response, in which the activation state of macrophages ((M1-M2 polarization) appears to play a critical role. Through this viewpoint, the immune system is responsible for isolating the implant biomaterial foreign body by forming bone around the oral implant effectively shielding off the implant from the host bone system, i.e. osseointegration becomes a continuous and dynamic host defense reaction. At the same time, this has led to the proposal of a new model of osseointegration, the foreign body equilibrium (FBE). In addition, as an oral wound, the soft tissues are involved with all their innate immune characteristics. When implant integration is viewed as an osteoimmune reaction, this has implications for how marginal bone is regulated. For example, while bacteria are constitutive components of the soft tissue sulcus, if the inflammatory front and immune reaction is at some distance from the marginal bone, an equilibrium is established. If however, this inflammation approaches the marginal bone, an immune osteoclastic reaction occurs and marginal bone is removed. A number of clinical scenarios can be envisioned whereby the osteoimmune equilibrium is disturbed and marginal bone loss occurs, such as complications of aseptic nature and the synergistic activation of pro-inflammatory pathways (implant/wear debris, DAMPs, and PAMPs). Understanding that an implant is a foreign body and that the host reacts osteoimmunologically to shield off the implant allows for a distinction to be drawn between osteoimmunological conditions and peri-implant bone loss. This review will examine dental implant placement as an osteoimmune reaction and its implications for marginal bone loss.

Prescription Drug Monitoring Program Use: National Dental PBRN Results.

INTRODUCTION: The American Dental Association recommends that dentists use a prescription drug monitoring program (PDMP) prior to prescribing an opioid for acute pain management. OBJECTIVE: The objective of this study was to examine dentists' experiences using their state PDMP, as well as the impact that state-mandated registration policies, mandated use policies, and practice characteristics had on the frequency with which dentists used their PDMP. METHODS: We conducted a web-based cross-sectional survey among practicing dentist members of the National Dental Practice-Based Research Network ( n = 805). The survey assessed prescribing practices for pain management and implementation of risk mitigation strategies, including PDMP use. Survey data were linked with network Enrollment Questionnaire data to include practitioner demographics and practice characteristics. RESULTS: Nearly half of respondents ( n = 375, 46.6%) reported having never accessed a PDMP, with the most common reasons for nonaccess being lack of awareness ( n = 214, 57.1%) and lack of knowledge regarding registration and use ( n = 94, 25.1%). The majority of PDMP users reported the program to be very helpful (58.1%) or somewhat helpful (31.6%). Dentists reported that PDMP use most often did not change their intended prescribing behavior (40.2%), led them not to prescribe an opioid (33.5%), or led them to prescribe fewer opioid doses (25.5%). Presence of a mandated use policy was significantly associated with increased frequency of PDMP use across a variety of situations, including prior to 1) prescribing any opioid for pain management, 2) issuing refills, 3) prescribing to new patients, and 4) prescribing to patients deemed high risk. CONCLUSION: Findings suggest that the majority of dentists find PDMPs helpful in informing their opioid-prescribing practices. Whereas the existence of a state-mandated use policy is a consistent predictor of dentists' PDMP use, outreach and education efforts may overcome key barriers to use identified in this study. KNOWLEDGE TRANSFER STATEMENT: Findings from this national survey suggest that the majority of practicing dentists find PDMPs helpful in informing their opioid-prescribing practices; however, consistent PDMP use was not common. Whereas the existence of a state-mandated use policy is a consistent predictor of dentists' PDMP use, outreach and education efforts may overcome key barriers to use identified in this study.

Effect of Osteotomy Preparation on Osseointegration of Immediately Loaded, Tapered Dental Implants.

The aim of the present preclinical in vivo study was to evaluate whether a modified "drill-only" protocol, involving slight underpreparation of the implant site, may have an effect on aspects of osseointegration of a novel bone-level tapered implant, compared with the "standard drilling" protocol involving taping and profiling of the marginal aspect of the implant socket. In each side of the edentulated and completely healed mandible of 11 minipigs, 2 tapered implants (8 mm long × 4.1 mm Ø, BLT; Institut Straumann AG, Basel, Switzerland) were installed either with the drill-only or the standard drilling protocol. Significantly lower average insertion torque values were recorded for the standard drilling protocol group (52 ± 29 Ncm) compared with the drill-only group (70 ± 27 Ncm) (t test, P ≤ 0.05); no significant difference was observed between the 2 groups regarding implant stability, by means of resonance frequency analysis (75 ± 8 vs. 75 ± 6, respectively). Half of the implants were immediately loaded and the rest were submerged, providing observation times of 8 or 4 wk, respectively. Non-decalcified histological and histomorphometric analysis of the implants with surrounding tissues showed no significant differences between the 2 drilling protocols regarding the distance from the implant platform to the first coronal bone-to-implant contact (f-BIC), the total bone-to-implant contact (BIC) as a percentage of the total implant perimeter, and the bone density in an area extending 1 mm laterally from the implant (BATA) within 2 rectangular regions of interest (ROIs) 4 mm in height, representing the coronal (parallel-walled) and apical (tapered) aspect of the implant (ROI 1 and ROI 2, respectively) in non-submerged implants. In general, marginal peri-implant bone levels were at or slightly apical to the implant platform, and large amounts of bone-to-implant contact were observed. In contrast, immediately loaded implants placed with the drill-only protocol showed statistically significantly lower BIC values (66% ± 13.7%) compared with those installed with the standard drilling protocol (74.8% ± 11.2%) (P = 0.018). In addition, although marginal bone levels were in most of the immediately loaded implants at or slightly apical to the implant platform, some of the implants installed with the drill-only protocol showed marginal bone loss and crater formation. Thus, in this model system, even slight underpreparation of the implant socket appeared to compromise osseointegration of immediately loaded bone-level tapered implants.

A Randomized Clinical Trial Evaluating rh-FGF-2/ß-TCP in Periodontal Defects.

Biological mediators have been used to enhance periodontal regeneration. The aim of this prospective randomized controlled study was to evaluate the safety and effectiveness of 3 doses of fibroblast growth factor 2 (FGF-2) when combined with a ß-tricalcium phosphate (ß-TCP) scaffold carrier placed in vertical infrabony periodontal defects in adult patients. In this double-blinded, dose-verification, externally monitored clinical study, 88 patients who required surgical intervention to treat a qualifying infrabony periodontal defect were randomized to 1 of 4 treatment groups-ß-TCP alone (control) and 0.1% recombinant human FGF-2 (rh-FGF-2), 0.3% rh-FGF-2, and 0.4% rh-FGF-2 with ß-TCP-following scaling and root planing of the tooth prior to a surgical appointment. Flap surgery was performed with EDTA conditioning of the root prior to device implantation. There were no statistically significant differences in patient demographics and baseline characteristics among the 4 treatment groups. When a composite outcome of gain in clinical attachment of 1.5 mm was used with a linear bone growth of 2.5 mm, a dose response pattern detected a plateau in the 0.3% and 0.4% rh-FGF-2/ß-TCP groups with significant improvements over control and 0.1% rh-FGF-2/ß-TCP groups. The success rate at 6 mo was 71% in the 2 higher-concentration groups, as compared with 45% in the control and lowest treatment groups. Percentage bone fill in the 2 higher-concentration groups was 75% and 71%, compared with 63% and 61% in the control and lowest treatment group. No increases in specific antibody to rh-FGF-2 were detected, and no serious adverse events related to the products were reported. The results from this multicenter trial demonstrated that the treatment of infrabony vertical periodontal defects can be enhanced with the addition of rh-FGF-2/ß-TCP (ClinicalTrials.gov NCT01728844).

Transcription factor and bone marrow stromal cells in osseointegration of dental implants.

Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone formation surrounding the implant is relatively slow after inserting the implant. The current study assessed the effects of bone marrow stromal cells (BMSCs) with forced expression of special AT-rich sequence-binding protein 2 (SATB2) on the osseointegration of titanium implants. To determine whether SATB2 overexpression in BMSCs can enhance the osseointegration of implants, BMSCs were infected with the retrovirus encoding Satb2 (pBABE-Satb2) and were locally applied to bone defects before implanting the titanium implants in the mouse femur. Seven and twenty-one days after implantation, the femora were isolated for immunohistochemical (IHC) staining, haematoxylin eosin (H&E) staining, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and micro-computed tomography (µCT) analysis. IHC staining analysis revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone tissue surrounding the implant. Histological analysis showed that SATB2-overexpressing BMSCs significantly enhanced new bone formation and bone-to-implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins in the implantation sites. µCT analysis demonstrated that SATB2-overexpressing BMSCs significantly increased the density of the newly formed bone surrounding the implant 3 weeks post-operatively. These results conclude that local delivery of SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium implants. These results provide support for future pharmacological and clinical applications of SATB2, which accelerates bone regeneration around titanium implants.

Rationalized assessment of prolonged jaundice is safe and cost-effective.

Prolonged jaundice (PJ) in healthy term neonates is common and frequently benign. It can, however, be the earliest manifestation of underlying liver disease. Its management requires a balanced approach, avoiding over-investigation of well babies while ensuring the early identification of those with pathology. Currently marked heterogeneity exists in the assessment of PJ. Over a two-year period we prospectively audited the management of PJ in two Level 3 neonatal units prior to and after the introduction of a rationalized investigation algorithm in keeping with the recently published British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) guidelines (i.e. clinical examination and stool inspection combined with measurement of split bilirubin). In this study we reviewed initial practice and then evaluated the impact of our change in practice. A total of 197 babies, 1.5% of live births, were referred with PJ. Of these, 105 babies were included in the first part of the study and 92 babies were included in the second part. No pathology relating to PJ, such as infection, hepatitis or liver disease, was identified. Following the introduction of our rationalized algorithm, we demonstrated a statistically significant reduction in the number of return appointments (28 versus 7; P < 0.0009) and repeat investigations (37 versus 7; P < 0.0001). This represented a saving of £1575-2625 per year in laboratory costs alone. Contemporaneously, three infants presented with biliary atresia, none of whom were identified by PJ screening and all of whom were over seven weeks old at diagnosis. A rationalized approach to the assessment of PJ reduces workload and is cost-effective; however, the limitations of selective screening, irrespective of how streamlined it is, remain--if babies are not identified and referred, they cannot be screened. Population-based methodologies offer an alternative approach to the identification of cholestatic liver disease and are worthy of further consideration.

The effect of targeted agents on outcomes in patients with brain metastases from renal cell carcinoma treated with Gamma Knife surgery.

OBJECT: Gamma Knife surgery (GKS) has been reported as an effective modality for treating brain metastases from renal cell carcinoma (RCC). The authors aimed to determine if targeted agents such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and bevacizumab affect the patterns of failure of RCC after GKS. METHODS: Between 1999 and 2010, 61 patients with brain metastases from RCC were treated with GKS. A median dose of 20 Gy (range 13-24 Gy) was prescribed to the margin of each metastasis. Kaplan-Meier analysis was used to determine local control, distant failure, and overall survival rates. Cox proportional hazard regression was performed to determine the association between disease-related factors and survival. RESULTS: Overall survival at 1, 2, and 3 years was 38%, 17%, and 9%, respectively. Freedom from local failure at 1, 2, and 3 years was 74%, 61%, and 40%, respectively. The distant failure rate at 1, 2, and 3 years was 51%, 79%, and 89%, respectively. Twenty-seven percent of patients died of neurological disease. The median survival for patients receiving targeted agents (n = 24) was 16.6 months compared with 7.2 months (n = 37) for those not receiving targeted therapy (p = 0.04). Freedom from local failure at 1 year was 93% versus 60% for patients receiving and those not receiving targeted agents, respectively (p = 0.01). Multivariate analysis showed that the use of targeted agents (hazard ratio 3.02, p = 0.003) was the only factor that predicted for improved survival. Two patients experienced post-GKS hemorrhage within the treated volume. CONCLUSIONS: Targeted agents appear to improve local control and overall survival in patients treated with GKS for metastastic RCC.

Engineered silica nanocarriers as a high-payload delivery vehicle for antioxidant enzymes.

Antioxidant enzymes for the treatment of oxidative stress-related diseases remain a highly promising therapeutic approach. As poor localization and stability have been the greatest challenges to their clinical translation, a variety of nanocarrier systems have been developed to directly address these limitations. In most cases, there has been a trade-off between the delivered mass of enzyme loaded and the carrier's ability to protect the enzyme from proteolytic degradation. One potential method of overcoming this limitation is the use of ordered mesoporous silica materials as potential antioxidant enzyme nanocarriers. The present study compared the loading, activity and retention activity of an anti-oxidant enzyme, catalase, on four engineered mesoporous silica types: non-porous silica particles, spherical silica particles with radially oriented pores and hollow spherical silica particles with pores oriented either parallel to the hollow core or expanded, interconnected bimodal pores. All these silica types, except non-porous silica, displayed potential for effective catalase loading and protection against the proteolytic enzyme, pronase. Hollow particles with interconnected pores exhibit protein loading of up to 50 wt.% carrier mass, while still maintaining significant protection against proteolysis.

Regeneration of periodontal tissues in non-human primates with rhGDF-5 and beta-tricalcium phosphate.

The application of growth factors has been advocated in support of periodontal regeneration. Recombinant human growth and differentiation factor-5 (rhGDF-5), a member of the bone morphogenetic protein family, has been used to encourage periodontal tissue regeneration. This study evaluated the dose response of rhGDF-5 lyophilized onto beta-tricalcium phosphate (bTCP) granules for periodontal tissue regeneration in a baboon model. Periodontal defects were created bilaterally in 12 baboons by a split-mouth design. Plaque was allowed to accumulate around wire ligatures to create chronic disease. After 2 mos, the ligatures were removed, and a notch was placed at the base of the defect. Two teeth on each side of the mouth were randomly treated with bTCP only, 0.5, 1.0, or 2.0 mg rhGDF-5/g bTCP. Animals were sacrificed 5 mos post-treatment, with micro-CT and histomorphometric analysis performed. After 5 mos, analysis showed alveolar bone, cementum, and periodontal ligament formation in all treatment groups, with a dose-dependent increase in rhGDF-5-treated groups. Height of periodontal tissues also increased with the addition of rhGDF-5, and the amount of residual graft material decreased with rhGDF-5 treatment. Therefore, rhGDF-5 delivered on bTCP demonstrated effective regeneration of all 3 tissues critical for periodontal repair.

Enhanced osseointegration of titanium implant through the local delivery of transcription factor SATB2.

Titanium implants are widely used in dentistry and orthopedic surgery. Nevertheless, bone regeneration around the implant is a relatively slow process, after placement. This study assessed whether SATB2 can enhance osseointegration of a titanium implant. To determine the effect of SATB2 in implant integration, two different viruses encoding SATB2 (PBABE-Satb2 virus or RCAS-Satb2 virus) were locally administered to the bone defect prior to titanium implant placement in our established transgenic TVA mice. Seven and 21 days post implantation, the femurs were isolated for quantitative real-time RT-PCR, H&E staining, immunohistochemical (IHC) staining, and microcomputed tomography (microCT) analysis. Quantitative real-time RT-PCR results demonstrated that the in vivo overexpression of SATB2 enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins. We also found that 21 days after implantation, there were no significant differences in the expression levels of SATB2, Osx, Runx2, COLI, OC, and BSP between the RCAS-Satb2 group and the RCAS group. Histological analysis showed that SATB2 overexpression significantly enhanced new bone formation and bone-to-implant contact after implantation. IHC staining analysis revealed that forced expression of SATB2 increased the number of BSP-positive cells surrounding the implant. MicroCT analysis demonstrated that in vivo overexpression of SATB2 significantly increased the density of the newly formed bone surrounding the implant. These results conclude that in vivo overexpression of SATB2 significantly accelerates osseointegration of titanium implants and SATB2 can serve as a potent molecule in promoting tissue regeneration.

Inflammation and uncoupling as mechanisms of periodontal bone loss.

Periodontal disease is characterized by both inflammation and bone loss. Advances in research in both these areas have led to a new appreciation of not only each field but also the intimate relationship between inflammation and bone loss. This relationship has resulted in a new field of science called osteoimmunology and provides a context for better understanding the pathogenesis of periodontal disease. In this review, we discuss several aspects of the immuno-inflammatory host response that ultimately results in loss of alveolar bone. A proposal is made that periodontal inflammation not only stimulates osteoclastogenesis but also interferes with the uncoupling of bone formation and bone resorption, consistent with a pathologic process. Furthermore, arguments based on experimental animal models suggest a critical role of the spatial and temporal aspects of inflammation in the periodontium. A review of these findings leads to a new paradigm to help explain more fully the impact of inflammation on alveolar bone in periodontal disease so that it includes the effects of inflammation on uncoupling of bone formation from resorption.

Impact of a Bereavement and Donation Service incorporating mandatory 'required referral' on organ donation rates: a model for the implementation of the Organ Donation Taskforce's recommendations.

In 2008 the Organ Donation Taskforce published its recommendations for increasing organ donation in the UK by 50% over 5 years. Bolton NHS Trust has addressed the problem of low rates of organ donation by amalgamating Bereavement and Donation Services and introducing a trigger to refer automatically all potential organ donors to the regional transplant donor co-ordinators. We audited the ability of the new service to deliver the aims and recommendations of the Organ Donation Taskforce. Following the changes in service provision the number of tissue donors rose from six in 2002 to 246 in 2007. In the same period solid organ donation rates remained unchanged. The introduction of an automatic trigger for referral of potential donors in 2007 resulted in 31 referrals and 11 successful multi-organ donors. The current service exceeds the aims of the Taskforce and offers the potential to meet UK organ donation targets without resorting to an 'opt out' system of presumed consent.

Recurrent torsades de pointes in association with a very low calorie diet.

The use of very low calorie diets under medical supervision is becoming increasingly popular in the UK, as the incidence of obesity continues to rise. We report the case of torsades de pointes developing during such a diet. Torsades de pointes has been reported in association with very low calorie diets in the past but to our knowledge, this is the first report since the introduction of newer, nutritionally complete versions of the diet. We review the intensive care management of recurrent torsades de pointes resistant to standard therapy and its relationship to dieting and obesity.

Integrin alpha2beta1 plays a critical role in osteoblast response to micron-scale surface structure and surface energy of titanium substrates.

Efforts to improve bone response to biomaterials have focused on ligands that bind alpha5beta1 integrins. However, antibodies to alpha5beta1 reduce osteoblast proliferation but do not affect differentiation when cells are grown on titanium (Ti). beta1-silencing blocks the differentiation stimulus of Ti microtopography, suggesting that other beta1 partners are important. Stably alpha2-silenced MG63 human osteoblast-like cells were used to test whether alpha2beta1 specifically mediates osteoblast response to Ti surface micron-scale structure and energy. WT and alpha2-silenced MG63 cells were cultured on tissue culture polystyrene (TCPS) and Ti disks with different surface microtopographies: machined pretreatment (PT) surfaces [mean peak to valley roughness (R(a)) < 0.02 microm], PT surfaces that were grit-blasted and acid-etched (SLA; R(a) = 4 microm), and SLA with high surface energy (modSLA). Alkaline phosphatase (ALP), alpha2 and beta1 mRNA, but not alpha5, alpha v, beta3, type-I collagen, or osteocalcin, increased on SLA and modSLA at 6 days. Alpha2 increased at 8 days on TCPS and PT, but remained unchanged on SLA and modSLA. Alpha2-protein was reduced 70% in alpha2-siRNA cells, whereas alpha5-mRNA and protein were unaffected. Alpha2-knockdown blocked surface-dependent increases in beta1 and osteocalcin and decreases in cell number and increases in ALP and local factors typical of MG63 cells grown on SLA and modSLA [e.g., prostaglandin E(2), osteoprotegerin, latent and active TGF-beta1, and stimulatory effects of 1alpha,25(OH)(2)D(3) on these parameters]. This finding indicates that alpha2beta1 signaling is required for osteoblastic differentiation caused by Ti microstructure and surface energy, suggesting that conclusions based on cell behavior on TCPS are not predictive of behavior on other substrates or the mechanisms involved.

Osteoblast response to fluid induced shear depends on substrate microarchitecture and varies with time.

Osteoblasts are exposed to fluid shear in vivo but the effects are not well understood, particularly how substrate properties or length of exposure modify the response. Short exposure (1 h) to shear reduces the stimulatory effect of micron-scale surface structure on osteoblast differentiation, but the effects of longer term exposures are not known. To test the hypothesis that substrate-dependent responses of osteoblasts to shear depend on the length of exposure to fluid flow, MG63 osteoblasts were grown on tissue culture glass, which has an average roughness (Ra) < 0.2 microm; machined Ti disks (PT, Ra < 0.6 microm); Ti disks with a complex microarchitecture [sand blasted acid etched (SLA), Ra = 4-5 microm); and Ti plasma-sprayed surfaces [Ti via plasma spray (TPS), Ra = 7 microm]. Confluent cultures were exposed to pulsatile flow at shear forces of 0, 1, and 14 dynes/cm(2) for 0, 6, 12, and 24 h. Shear reduced cell number on all surfaces, with greatest effects on TPS. Shear had no effect on alkaline phosphatase on smooth surfaces but increased enzyme activity on SLA and TPS in a time-dependent manner. Its effects on osteocalcin, TGF-beta1, and PGE(2) in the conditioned media were greatest on these surfaces as well. Responses to fluid-induced shear were blocked by the general Cox inhibitor indomethacin and the Cox-2 inhibitor meloxicam, indicating that response to shear is mediated by prostaglandin produced via a Cox-2 dependent mechanism. These results show that the effects of fluid induced shear change with time and are substrate dependent, suggesting that substrate microarchitecture regulates the osteoblast phenotype and effects of shear are determined by the maturation state of the responding population.

Phase I clinical trial results of verteporfin enhanced feeder vessel therapy in subfoveal choroidal neovascularisation in age related macular degeneration.

AIMS: To investigate the safety and effectiveness of extrafoveal photodynamic therapy (PDT) occlusion of feeder vessels (FVs) in patients with subfoveal choroidal neovascularisation (CNV) as a result of age related macular degeneration. METHODS: FVs were identified using dynamic fluorescein and indocyanine green angiography with scanning laser ophthalmoscope. The standard doses of verteporfin and laser wavelength were used. The light dose was escalated by increasing the duration of the light dose so the light regimen was 50 J/cm2 for patients 1 and 2; 100 J/cm2 for patients 3, 4, 5; 125 J/cm2 for patients 6 and 7; and 150 J/cm2 for patients 8 and 9. Patients were examined at weeks 1, 4, and 12. RESULTS: The mean improvement on EDTRS chart 3 months after treatment was an increase of 2.1 lines (p = 0.07). Closure of the FV was achieved angiographically in three eyes at various light doses, in three eyes the FV was hypoperfused, and in three eyes the vessels were were neither closed nor hypoperfused. At the last follow up all FVs were reperfused. There was no evidence of retinal damage. CONCLUSION: Verteporfin enhanced FV therapy does not cause subfoveal retinal damage and may have potential to improve central vision in subfoveal CNV caused by exudative macular degeneration. It is not recommended as a monotherapy for CNV.

Peri-implant inflammation defined by the implant-abutment interface.

An implant-abutment interface at the alveolar bone crest is associated with sustained peri-implant inflammation; however, whether magnitude of inflammation is proportionally dependent upon interface position remains unknown. This study compared the distribution and density of inflammatory cells surrounding implants with a supracrestal, crestal, or subcrestal implant-abutment interface. All implants developed a similar pattern of peri-implant inflammation: neutrophilic polymorphonuclear leukocytes (neutrophils) maximally accumulated at or immediately coronal to the interface. However, peri-implant neutrophil accrual increased progressively as the implant-abutment interface depth increased, i.e., subcrestal interfaces promoted a significantly greater maximum density of neutrophils than did supracrestal interfaces (10,512 +/- 691 vs. 2398 +/- 1077 neutrophils/mm(2)). Moreover, inflammatory cell accumulation below the original bone crest was significantly correlated with bone loss. Thus, the implant-abutment interface dictates the intensity and location of peri-implant inflammatory cell accumulation, a potential contributing component in the extent of implant-associated alveolar bone loss.

Biomechanical evaluation of the interfacial strength of a chemically modified sandblasted and acid-etched titanium surface.

The functional capacity of osseointegrated dental implants to bear load is largely dependent on the quality of the interface between the bone and implant. Sandblasted and acid-etched (SLA) surfaces have been previously shown to enhance bone apposition. In this study, the SLA has been compared with a chemically modified SLA (modSLA) surface. The increased wettability of the modSLA surface in a protein solution was verified by dynamic contact angle analysis. Using a well-established animal model with a split-mouth experimental design, implant removal torque testing was performed to determine the biomechanical properties of the bone-implant interface. All implants had an identical cylindrical shape with a standard thread configuration. Removal torque testing was performed after 2, 4, and 8 weeks of bone healing (n = 9 animals per healing period, three implants per surface type per animal) to evaluate the interfacial shear strength of each surface type. Results showed that the modSLA surface was more effective in enhancing the interfacial shear strength of implants in comparison with the conventional SLA surface during early stages of bone healing. Removal torque values of the modSLA-surfaced implants were 8-21% higher than those of the SLA implants (p = 0.003). The mean removal torque values for the modSLA implants were 1.485 N m at 2 weeks, 1.709 N m at 4 weeks, and 1.345 N m at 8 weeks; and correspondingly, 1.231 N m, 1.585 N m, and 1.143 N m for the SLA implants. The bone-implant interfacial stiffness calculated from the torque-rotation curve was on average 9-14% higher for the modSLA implants when compared with the SLA implants (p = 0.038). It can be concluded that the modSLA surface achieves a better bone anchorage during early stages of bone healing than the SLA surface; chemical modification of the standard SLA surface likely enhances bone apposition and this has a beneficial effect on the interfacial shear strength.

High surface energy enhances cell response to titanium substrate microstructure.

Titanium (Ti) is used for implantable devices because of its biocompatible oxide surface layer. TiO2 surfaces that have a complex microtopography increase bone-to-implant contact and removal torque forces in vivo and induce osteoblast differentiation in vitro. Studies examining osteoblast response to controlled surface chemistries indicate that hydrophilic surfaces are osteogenic, but TiO2 surfaces produced until now exhibit low surface energy because of adsorbed hydrocarbons and carbonates from the ambient atmosphere or roughness induced hydrophobicity. Novel hydroxylated/hydrated Ti surfaces were used to retain high surface energy of TiO2. Osteoblasts grown on this modified surface exhibited a more differentiated phenotype characterized by increased alkaline phosphatase activity and osteocalcin and generated an osteogenic microenvironment through higher production of PGE2 and TGF-beta1. Moreover, 1alpha,25OH2D3 increased these effects in a manner that was synergistic with high surface energy. This suggests that increased bone formation observed on modified Ti surfaces in vivo is due in part to stimulatory effects of high surface energy on osteoblasts.