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INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co‐organized and co‐sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. DISCUSSION: The virtual meeting provided an opportunity to foster cross‐sector collaboration and partnerships as well as a forum for updating colleagues on research‐advancing tools and programs that are steadily moving the field forward. [ABSTRACT FROM AUTHOR]

Background: Current understanding of the clinical features of persons with melorheostosis is restricted primarily to individual case reports and small case series.Objective: To assess the clinical features of patients with melorheostosis treated at our institution from 1972 through 2010.Design: Chart review.Setting: Tertiary academic medical center.Participants: Twenty-three patients with "definite" and one patient with "probable" melorheostosis based on radiographic criteria.Methods: The eligible study cohort was identified through the Rochester Medical Index database. Further diagnostic confirmation of patients with melorheostosis was performed by radiographic review.Main Outcome Measurements: We evaluated age at first visit to our institution, gender, affected body area, number of bones affected, presenting symptoms, surgical evaluation, and therapies provided.Results: The average age at first evaluation at our clinic was 36.5 years (median 41.5 years, range 3-68 years). The female to male ratio was 4:1. The lower extremity was most commonly affected (66.6%), followed by upper extremity (33.3%), spine (16.6%), and head (8.3%). One-third of patients had involvement of a single bone; two-thirds had multiple bone involvement. Pain was the most common presenting concern (83.3%), followed by deformity (54.1%), limitation of movement (45.8%), numbness (37.5%), and weakness (25.0%). Most patients had a physician evaluation (87.5%); patients also underwent orthopedic surgery (45.8%), physical therapy (33.3%), and occupational therapy (12.5%).Conclusions: Melorheostosis is a rare sclerotic bone disease resulting in pain, deformity, and dysfunction. An interdisciplinary approach to care should include nonoperative and operative evaluation, as well as appropriate therapies. A prospective approach to evaluation, including imaging and physical examinations, would provide valuable longitudinal data.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

Background: OnabotulinumtoxinA reduces muscle hypertonia associated with poststroke spasticity (PSS). PSS manifests as several common postures.Objective: To define treatment paradigms for PSS upper-limb common postures.Design: Modified Delphi method.Setting: Expert panel.Participants: Ten injectors experienced in the treatment and clinical research of PSS (physiatrists and neurologists) were invited to participate in the Delphi panel.Methods: The Delphi panel reviewed an electronic worksheet with PSS upper-limb postures to define onabotulinumtoxinA treatment paradigms (Round 1). During Round 2, panel members discussed in person Round 1 results and voted until consensus (≥66% agreement). Recommendations were geared toward those with new or early injection experience.Main Outcome Measurements: Expert consensus on onabotulinumtoxinA treatment parameters for PSS including muscles to inject, dose per muscle and posture, and treatment adjustments for suboptimal response.Results: For each posture, consensus was reached on targeted subsets of muscles. Doses ranged for individual muscles (10-100 U) and total doses per posture (50-200 U). An onabotulinumtoxinA dilution 50 U/mL (2:1 dilution ratio) was considered most appropriate; dilution ratios of 1:1 to 4:1 may be appropriate in some circumstances. The majority (89%) of panel members would increase the dose and/or the number of muscles treated for a suboptimal response to onabotulinumtoxinA. The panel identified 3 common aggregate upper-limb postures: (1) adducted shoulder + flexed elbow + pronated forearm + flexed wrist + clenched fist; (2) flexed elbow + pronated forearm + flexed wrist + clenched fist; and (3) flexed wrist + clenched fist. The recommended starting dose per aggregate was 300 U, 300 U, and 200 U, with a total maximum dose of 400 U, 400 U, and 300 U, respectively. Localization guidance techniques were considered essential for all postures.Conclusions: Consensus on common muscles and onabotulinumtoxinA treatment paradigms for postures associated with upper-limb PSS was achieved via a modified Delphi method. The purpose of this analysis is to educate early onabotulinumtoxinA injectors rather than provide an evidence-based review.Level Of Evidence: V. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of botulinum toxin type A (BoNT-A) injected intra-articularly in 60 subjects with moderate pain and functional impairment secondary to knee osteoarthritis. The study investigators hypothesized that intra-articular BoNT-A would result in statistically significant improvements in pain and function at 8 weeks. Design: Double-blind, randomized, single tertiary care academic medical center trial with 6-month follow-up. Patients: Sixty patients aged 40 years or older with painful osteoarthritis of the knee who had failed physical therapy, medications, and/or injection therapy presenting to the musculoskeletal or orthopedic outpatient clinics at a large tertiary care medical institution. All 60 patients completed 8-week follow-up, but only 32 patients completed the 26-week follow-up. Methods: Subjects were randomized to receive a single injection of corticosteroid, low-dose BoNT-A (100 units), or high-dose BoNT-A (200 units). Outcome measures were compared at baseline, 4, 8, 12, and 26 weeks after injection. Main Outcome Measurements: The primary outcome measure was pain visual analog scale (VAS) at 8 weeks. Secondary outcome measures included Western Ontario McMaster Arthritis Index, Short Form-36 scores, patient global assessment, 40-meter timed walk, and adverse effects. Results: The primary end point was pain VAS score at 8 weeks, which decreased within each group but only reached statistical significance in the low-dose BoNT-A group. In the intra-articular corticosteroid group, VAS decreased from 6.4 ± 1.8 to 5.4 ± 2.3 (P = .15); for low-dose BoNT-A, from 6.6. ± 1.9 to 4.5 ± 2.2 (P = .01); and for high-dose BoNT-A, from 6.6 ± 1.4 to 5.9 ± 2.4 (P = .15). All groups showed statistically significant improvements in Western Ontario McMaster Arthritis Index scores (pain, stiffness, function) at 8 weeks. No serious adverse events were noted in any group. Conclusions: This pilot study supports a possible role for BoNT-A as a treatment option for symptomatic knee osteoarthritis; however, larger double-blind randomized studies are needed to determine whether BoNT-A is more effective than placebo in this patient population. [Copyright &y& Elsevier]

Background: An earlier publication from our laboratory described the use of guided bone regeneration to fill large bone voids in the mandible created through en bloc resection in primates. The present report is an embellishment of this paper and describes bone regeneration experiments in 18 adult male Macaca mulatta monkeys to determine how long membranes must be in position to promote guided bone regeneration. Methods: Thirty-six lesions were created in the mandibles of 18 monkeys in a standardized mandibular defect of 8 x 19 mm. Reinforced ePTFE membranes were placed in the animals and held in place with mini screws and sutures for anywhere from 1 to 12 months. No material was added to the defect. In addition to clinical studies, digital subtraction radiology and fluorescent labeling with tetracycline and histomorphometry are described. Results: The results indicate that no bone gain was observed in membranes exposed for 1 month or less, but bone gain (approximately well over 90% of defects) was observed at 12 months when membranes were left in situ for 2 to 12 months (P <0.0001). No significant difference in the amount of bone gained at 12 months was observed for membranes left in place for intervals ranging from 2 to 12 months. A significant correlation between the amount of bone gain observed at 3 and 12 months was observed (P <0.0001). Conclusions: Data therefore suggest that membranes left in situ for 1 month or less result in minimal bone gain compared with membranes left in place from 2 to 12 months. In addition, labeling and stained sections clearly showed that the bone produced after 2 months of membrane placement is mature. [ABSTRACT FROM AUTHOR]

Background: Polymorphonuclear leukocytes (PMNs) take up and accumulate ciprofloxacin. This may allow them to enhance the delivery of this agent to the inflamed periodontium.Methods: Cross-sectional and longitudinal approaches were used to test the hypothesis. In the cross-sectional study, 7 periodontally healthy adults and 8 adults with untreated periodontitis were administered three doses of ciprofloxacin (500 mg bid). Gingival fluid (GF) and serum samples were obtained after 28 hours and analyzed by high-performance liquid chromatography (HPLC). In the longitudinal study, 8 adult periodontitis subjects were administered 500 mg ciprofloxacin bid for 8 days. After 28 hours, GF from 4 sites with 5 to 8 mm probing depths was sampled in each subject, serum samples were obtained, and 2 of the 4 sites were root planed. GF and serum were sampled again 7 days later (196 hours after the initial dose).Results: The mean ciprofloxacin levels in the GF and serum of periodontally healthy subjects were 2.52 +/- 0.22 microg/ml and 0.47 +/- 0.05 microg/ml, respectively. In subjects with periodontitis, these levels were 2.69 +/- 0.44 microg/ml and 0.61 +/- 0.13 microg/ml, respectively. GF ciprofloxacin levels were significantly higher than corresponding serum levels in healthy and diseased subjects (P<0.01), but there were no significant differences in GF or serum levels between the 2 subject groups. Since GF flow was significantly higher at diseased sites, however, more ciprofloxacin was distributed to these sites than to healthy sites. In the longitudinal study, GF flow at 196 hours was 16% lower at root planed sites than at untreated control sites (P = 0.412). The minor decrease in this index of inflammation was accompanied by a small (9%), but statistically significant (P= 0.007), decrease in GF ciprofloxacin levels.Conclusions: GF ciprofloxacin levels decreased slightly at inflamed periodontal sites after root planing, but were significantly higher than serum levels even at healthy periodontal sites. Inflammation may enhance the distribution of ciprofloxacin to diseased sites, but it is not a major determinant of GF ciprofloxacin levels. [ABSTRACT FROM AUTHOR]

The posterior maxilla has traditionally been one of the most difficult areas to successfully place dental implants due to poor bone quality and close approximation to the maxillary sinus. Sinus augmentation procedures have become a viable means of assuring adequate bone for the placement of dental implants in this area. However, with the techniques currently employed, a considerable variation in the quality of bone attained with the sinus augmentation procedure exists. The purpose of this in vivo study was to evaluate the healing response and bone formation stimulated by 3 doses of recombinant human osteogenic protein-1 (rhOP-1), 0.25, 0.6, and 2.5 mg OP-1 per gram of collagen matrix; natural bone mineral; or collagen matrix alone (control) placed in the maxillary sinus of adult chimpanzees. Results were assessed using clinical, histologic, and radiographic techniques. Radiographic analysis of the computed tomography scans taken at 1 week, and 2.5, 4.5, and 6.5 months revealed a more rapid mineralization with the 2.5 mg OP-1/g collagen matrix and natural bone mineral treatment groups. The incremental bone mineral density (BMD) increase for these 2 treatments from 1 week to 2.5 months was over 2.5 times the increase found with the collagen matrix alone; these 2 treatments also had a higher BMD at the most superior slices evaluated when compared to the other 3 groups. Biopsy specimens were taken at 3.5, 5.5, and 7.5 months and for all 5 treatment groups bone formation was observed at all time points in the majority of the specimens. At 7.5 months the 2.5 and 0.6 mg OP-1/g collagen matrix treatment groups had an increase in the percent bone area when compared to the matrix alone control. In conclusion, these results demonstrate that sinus augmentation with natural bone mineral or 2.5 mg OP-1/g collagen matrix induce comparable radiographic and histologic evidence of bone formation and that both of these treatments performed superior to the control group of collagen matrix alone based upon all methods of evaluation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Randomized controlled trials (RCTs) provide safety and efficacy data for regulatory approval of antidementia drugs, but offer limited data regarding real-world effectiveness. Long-term observational controlled studies (LTOCs) extend our understanding by providing longitudinal data across multiple stages of Alzheimer’s disease (AD). Methods: Comparisons of strengths, limitations, evidence level, and results for monotherapy (cholinesterase inhibitors) and combination therapy (cholinesterase inhibitors + memantine) in RCTs versus LTOCs were made. Results: Similar to RCTs, LTOCs have shown that both monotherapy and combination therapy are associated with slower cognitive and functional decline. Combination therapy is associated with better cognitive outcomes and greater delays in time to nursing home admission versus monotherapy or no treatment. Persistent antidementia drug treatment is associated with slower decline in cognition, daily function, and global severity, even in patients with advanced disease. Conclusions: LTOCs provide complementary evidence regarding effectiveness of antidementia therapy over many years, a time course relevant to AD management. These findings also provide compelling arguments in favor of using LTOCs to estimate effectiveness, risk–benefit, and costs of AD treatments. [Copyright &y& Elsevier]

Objective: To critically review the best available studies evaluating the efficacy of lumbosacral transforaminal epidural steroid injections (TFESIs) in the treatment of radicular pain. Data Sources: MEDLINE, EMBASE, and the Cochrane database were searched for the period between 1950 and May 2008. Search terms included epidural steroid injection (ESI), transforaminal ESI, foraminal ESI, selective nerve root block, nerve root injection (NRI), selective NRI, periradicular infiltration, and periradicular injection. Randomized controlled trials (RCTs), published in English, which evaluated the efficacy of fluoroscopically guided TFESIs were reviewed. Study Selection: Studies were analyzed with a quality checklist modeled after the 2001 CONSORT Statement: Revised Recommendations for Improving the Quality of Reports of Parallel-Group Randomized Trials. Nine studies were found to include a majority of these items. Data Extraction: Data included study design, inclusion criteria, symptom duration, randomization protocol, blinding protocol, intervention, control, outcomes, follow-up, dropout, statistical analysis, and conclusions. Data Synthesis: Each article was assigned a level of evidence: I (high-quality RCT) or II (RCT with <80% follow-up, no blinding or improper randomization). Studies were divided according to control, and overall evidence was graded as A (good), B (fair), C (conflicting/poor quality), or I (insufficient). Conclusions: There is fair evidence supporting TFESIs as superior to placebo for treating radicular symptoms. There is good evidence that TFESIs should be used as a surgery-sparing intervention, and that TFESIs are superior to interlaminar ESIs (ILESIs) and caudal ESIs for radicular pain. In patients with subacute or chronic radicular symptoms, there is good evidence that a single TFESI has similar efficacy as a single transforaminal injection of bupivacaine or saline. Future studies should address the ideal number of injections. While more placebo-controlled trials are needed to conclusively define the role of TFESIs, current studies support their use in the treatment of lumbosacral radicular pain. [Copyright &y& Elsevier]

Background: Myeloid sarcoma is an extramedullary malignancy of myetoblasts. An unusual case of myeloid sarcoma presenting in the gingiva and affected by drug-induced gingival enlargement is presented. Methods: A 63-year-old male taking amlodipine for his hypertension presented with a 3-week gingival enlargement. Although the obvious clinical impression was that of drug-induced gingival enlargement, an incisional biopsy was performed to corroborate chemical enlargement while ruling out diseases such as lymphoma and leukemia. Results: Microscopic examination of the thickened gingiva revealed surface stratified squamous epithelium having needle-like rete pegs characteristic of drug-induced gingival enlargement. Beneath the surface epithelium, the fibrous tissue was virtually replaced by a dense infiltrate of malignant cells. Immunohistochemical studies were performed with CD117 and myeloperoxidase identifying the malignant cell population as myeloblasts, leading to a diagnosis of myeloid sarcoma. Conclusion: Myeloid sarcoma and hematopoietic malignancies must be included in a differential diagnosis of gingival enlargement until the definitive diagnosis is reached by histologic/laboratory examination. [ABSTRACT FROM AUTHOR]

Background: This study measured the ability of three toothbrushes to remove plaque following three single brushing episodes with each toothbrush. Methods: This was a randomized, controlled, examiner-blind, nine period crossover study conducted in 72 adult subjects over a 3 month period that examined plaque removal with a rechargeable power toothbrush and two manual toothbrushes. During the course of this study, subjects brushed three times with each of the toothbrushes. Plaque was scored before and after brushing using the Rustogi Modification of the Navy Plaque Index. Results: Average baseline plaque scores were between 0.373 and 0.376 for the three treatment groups. The power toothbrush delivered an adjusted (via analysis of covariance) mean difference between baseline and post-brushing plaque scores of 0.270, whereas the manual toothbrushes delivered adjusted mean differences of 0.211 (control ADA manual toothbrush) and 0.190 (experimental manual toothbrush), The power toothbrush demonstrated a statistically significantly greater reduction in plaque than the ADA reference manual toothbrush (P<0.001), which in turn had a statistically significantly greater reduction in plaque than the experimental manual toothbrush (P<0.001). The powered toothbrush group had, on average, 42.4% and 28.2% greater plaque removal scores than the experimental manual toothbrush and ADA reference manual toothbrush groups, respectively. Results for the interproximal and gingival regions also demonstrated statistically significantly (P <0.001) greater plaque removal for the powered toothbrush relative to the control manual toothbrushes. Conclusion: The powered toothbrush was found to deliver greater plaque removal by 42.4% and 28.2% compared to the control manual toothbrushes. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to evaluate clinically and under scanning electron microscopy (SEM) the efficacy of Nd:YAG laser irradiation alone and in combination with 5% sodium fluoride varnish in the management of dentin hypersensitivity. Methods: The study was conducted on 40 patients divided into four groups who had at least one tooth of Grade III mobility with clinically elicitable dentin hypersensitivity. Following the pretreatment assessment of hypersensitivity using the visual analog scale (VAS) and cold air blast test, the selected tooth in all the groups received 1% citric acid treatment for 1 minute. Group 1 patients received no further treatment; group 2, 3, and 4 patients received additional treatment with 5% sodium fluoride varnish, Nd:YAG laser for 2 minutes, and a combination of 5% sodium fluoride varnish and Nd:YAG laser, respectively. Two hours following treatment, hypersensitivity was again assessed, and the teeth were extracted, sectioned, and scanned using scanning electron microscopy (SEM). Results: The mean VAS score in group 1 showed a 27% increase from baseline, but groups 2, 3, and 4 showed a decrease of 33%, 44%, and 62%, respectively. The mean cold air blast score showed a 22% increase in group 1, but values decreased by 43%, 50%, and 83% in groups 2, 3, and 4, respectively. The number of patent tubules also progressively decreased from group 1 through group 4. Conclusions: The combination of Nd:YAG laser and 5% sodium fluoride varnish seems to show an impressive efficacy, when compared to either treatment alone, in treating dentin hypersensitivity. The SEM findings seem to relate to the clinical findings in that reduction in number/patency of tubules was associated with improvement in treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the efficacy, relative safety, and tolerability of 1% pimecrolimus cream in the treatment of oral erosive lichen planus (OELP). Methods: Twenty patients with OELP were randomized into equal groups; group 1 applied 1% pimecrolimus cream twice daily to their oral lesions for 4 weeks, whereas group 2 applied a placebo cream, Photographs of the lesions were taken and analyzed for areas of ulceration, erythema, and reticulation. Discomfort scores were also assessed with a visual analogue scale (VAS). Blood samples were taken at baseline and at study completion; a complete blood count with differential and comprehensive metabolic panel was ordered. The Wilcoxon signed rank test was used. Results: The experimental group showed a decrease in ulceration (α = 0.068) and erythema (α = 0.005) at the mid-point with continued reduction of erythema at the final (α = 0.075) time measurement. The control group demonstrated an increase in reticulation at the mid-point (α = 0.017) and final (α = 0.007) time measurement. The VAS scores for the experimental group decreased during the study (α = 0.022). Blood levels were within the normal range. Conclusions: The OELP lesion size in the 1% pimecrolimus group decreased and the pimecrolimus cream was found to significantly reduce the patient's pain scores. Further study of 1% pimecrolimus as therapy for OELP is warranted since it was shown to be effective, relatively safe, and well tolerated by patients within the limits of this short-term study. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the inhibitory activity of triphala on PMN-type matrix metalloproteinase (MMP-9) expressed in adult periodontitis patients and compared its activity with another ayurvedic drug, kamillosan, and doxycycline, which has known inhibitory activity. Methods: Matrix metalloproteinases (MMPs) were extracted from gingival tissue samples from 10 patients (six males, four females) with chronic periodontitis. Tissue extracts were treated with the drug solutions, the inhibition was analyzed by gelatin zymography, and the percentage of inhibition was determined by a gel documentation system. Results: The activity of MMPs was significantly decreased with the use of the drugs. Triphala showed a 76,6% reduction of MMP-9 activity, whereas kamillosan showed a 46.36% reduction at a concentration of 1,500 µg/ml (crude extract) and doxycycline showed a 58.7% reduction at a concentration of 300 µg/ml (pure drug). Conclusion: The present study showed the strong inhibitory activity of triphala on PMN-type MMPs involved in the extracellular matrix (ECM) degradation during periodontitis. [ABSTRACT FROM AUTHOR]

The article presents information on cytokine gene polymorphism and immunologist in periodontal disease. Understanding what triggers inappropriate tissue destructive host responses is central to providing rational diagnostic and therapeutic strategies for this condition. It is clear that there is significant individual variation in the development and progression of periodontitis. The genetic element for periodontal disease, a central pathogenic role for cytokines, as well as the principle of individual variation in disease experience are tenets of periodontal research. However, a role for cytokine gene polymorphism in immunoregulation in periodontal disease remains suggestive rather than being firmly established.

Background: A recent Phase 3 trial demonstrated that adjunctive treatment with minocycline microspheres resulted in significant reductions in patient mean probing depths as compared to scaling and root planing (SRP) alone. The objective of the present study was to evaluate clinical relevance of these changes within the trial using proposed site-based criteria. Methods: A total of 499 patients with moderate to advanced chronic periodontitis were enrolled in a multi-center trial and randomized to either: 1) SRP alone or 2) SRP plus minocycline microspheres. Subjects received complete probing examinations including the measurement of probing depths at baseline, and 1 and 3 months. Probing depth reductions were tabulated by treatment, examination time, and baseline depths, and intergroup differences were evaluated with logistic regression models for correlated data. Results: Significantly more sites treated with adjunctive minocycline microspheres exhibited probing depths <5 mm at 1 (P = 0.0009) and 3 (P = 0.01) months as compared to sites treated with SRP alone, both in the overall population and in smokers. In addition, significantly more sites decreased by 1, 2, or 3 mm in the adjunctive minocycline group than in the SRP alone group at 1 and 3 months, both overall as well as in smokers (P <0.05). Conclusion: This secondary analysis indicates that treatment with SRP plus minocycline microspheres is consistently more effective than SRP alone in providing clinically relevant site-based responses in patients with chronic periodontitis. [ABSTRACT FROM AUTHOR]

Background: Medical-grade calcium sulfate (CS) is a biocompatible, bioabsorbable, and clinically versatile ceramic for use in bone repair. This study compared the clinical efficacy of a combination of calcium sulfate dihydrate, as a binder and barrier, and demineralized freeze-dried bone allograft (DFDBA) to polytetrafluoroethylene (ePTFE) and DFDBA for the treatment of human periodontal defects. Methods: Two intrabony defects were compared in each of 19 patients with chronic periodontitis. After initial preparation, full-thickness mucoperiosteal flaps were elevated, osseous defects debrided, and the roots prepared (ultrasonic, hand curets, and tetracycline conditioning). Defects were randomly treated with either a combination graft of DFDBA with CS (4:1) covered by a CS barrier or with DFDBA and fitted with an ePTFE barrier. Flaps were coronally positioned to obtain primary closure. Clinical soft tissue measurements were recorded at 6 months, and all study sites were surgically reentered for evaluation. Results: The mean presurgical measurements for defects randomized to the CS and ePTFE treatments, respectively, were similar for attachment level (AL; 6.2 ± 1.8 mm and 6.1 ± 1.7 mm), probing depth (PD; 6.3 ± 1.1 mm and 6.2 ± 1.1 mm), and gingival recession (0.1 ± 1.9 mm and 0.2 ± 1.4 mm). Defects treated with CS or ePTFE demonstrated statistically significant (P ≤0.0001) reductions in mean PD (2.7 ± 1.4 mm and 3.4 ± 1.3 mm, respectively) and gains in mean AL (1.8 ± 1.5 mm and 1.7 ± 1.4 mm, respectively). Recession increased by 0.8 ± 1.4 mm at CS sites and 1.6 ± 1.7 mm at ePTFE-treated sites (P ≤0.05). Pretreatment mean defect depths were 4.1 ± 1.0 mm and 3.7 ± 1.0 mm for CS and ePTFE sites, respectively. Reentry evaluations revealed a mean defect fill of 2.7 ± 1.5 mm and 2.5 ± 0.9 mm for the CS and ePTFE sites, respectively, with a corresponding mean defect resolution of 80.3 ± 18.7% and 76.7 ± 18.5%. The CS and ePTFE sites did not differ significantly in mean defect fill or defect resolution. Conclusions: The results of this study indicate that calcium sulfate, when used as a binder and barrier in combination with DFDBA, supports significant clinical improvement in intrabony defects, as evidenced by reductions in probing depth, gains in clinical attachment level, and defect fill and resolution. Calcium sulfate represents an important alternative to non-resorbable ePTFE barriers in combination with DFDBA for the treatment of intrabony defects. [ABSTRACT FROM AUTHOR]

Background: Calcium hydroxyapatite cement (HAC) has been demonstrated in both animal models and human craniofacial defects to be safe, absorbable, osteoconductive, and possibly osteoinductive. This pilot study evaluated a novel technique using HAC to surgically obturate Class III mandibular molar furcation defects. Methods: Following flap reflection, affected teeth in 6 patients were root planed and etched with citric acid. Experimental sites were grafted with HAC and coronally positioned flaps (CPF), while controls were treated by CPF only. A variety of clinical parameters were recorded initially, and at re-entry surgery 9 months later. Results: At re-entry, all experimental sites exhibited granulation tissue interposed between the HAC and the alveolar bone, and clinical findings were unsatisfactory. Mean probing depth, clinical attachment loss, and recession increased by 0.8 mm, 1.9 mm, and 1.2 mm, respectively, in experimental sites. In controls, mean probing depth decreased by 0.8 mm, and clinical attachment loss and recession increased by 0.3 mm and 1.2 mm, respectively. There was a mean 1.6 mm loss in osseous crest height and a mean 2.2 mm worsening in osseous defect depth for experimental sites, but only a 0.5 mm loss in osseous crest and 0.5 mm increase in osseous defect depth in control sites. Conclusions: Experimental sites lost 1.0 to 1.5 mm in bone and attachment compared to controls, without any significant clinical benefit. While the concept of surgically obturating Class III furcation defects with a safe, osteoconductive material remains attractive, HAC did not promote repair or regeneration in this technique. [ABSTRACT FROM AUTHOR]

Background: Endosseous implants can be placed according to a non-submerged or submerged approach and in 1- or 2-piece configurations. Recently, it was shown that peri-implant crestal bone changes differ significantly under such conditions and are dependent on a rough/smooth implant border in 1-piece implants and on the location of an interface (microgap) between the implant and abutment/restoration in 2-piece configurations. Several factors may influence the resultant level of the crestal bone under these conditions, including movements between implant components and the size of the microgap (interface) between the implant and abutment. However, no data are available on the impact of possible movements between these components or the impact of the size of the microgap (interface). The purpose of this study was to histometrically evaluate crestal bone changes around unloaded, 2-piece non-submerged titanium implants with 3 different microgap (interface) dimensions and between implants with components welded together or held together by a transocclusal screw. Methods: A total of 60 titanium implants were randomly placed in edentulous mandibular areas of 5 hounds forming 6 different implant subgroups (A through F). In general, all implants had a relatively smooth, machined suprabony portion 1 mm long, as well as a rough, sandblasted, and acid-etched (SLA) endosseous portion, all placed with their interface (microgap) 1 mm above the bone crest level and having abutments connected at the time of first-stage surgery, implant types A, B, and C had a microgap of <10 µm, ~50 µm, or ~100 µm between implant components as did types D, E, and F, respectively. As a major difference, however, abutments and implants of types A, B, and C were laser-welded together, not allowing for any movements between components, as opposed to types D, E, and F, where abutments and implants were held together by abutment screws. Three months after implant placement, all animals were sacrificed. Non-decalcified histology was analyzed histometrically by evaluating peri-implant crestal bone changes. Results: For implants in the laser-welded group (A, B, and C), mean crestal bone levels were located at a distance from the interface (IF; microgap) to the first bone-to-implant contact (fBIC) of 1.06 ± 0.46 mm (standard deviation) for type A, 1.28 ± 0.47 mm for type B, and 1.17 ± 0.51 mm for type C. All implants of the non-welded group (D, E, and F) had significantly increased amounts of crestal bone loss, with 1.72 ± 0.49 mm for type D (P<0.01 compared to type A), 1.71 ± 0.43 mm for type E (P <0.02 compared to type B), and 1.65 ± 0.37 mm for type F (P<0.01 compared to type C). Conclusions: These findings demonstrate, as evaluated by non-decalcified histology under unloaded conditions in the canine mandible, that crestal bone changes around 2-piece, non-submerged titanium implants are significantly influenced by possible movements between implants and abutments, but not by the size of the microgap (interface). Thus, significant crestal bone loss occurs in 2-piece implant configurations even with the smallest-sized microgaps (<10 µm) in combination with possible movements between implant components. [ABSTRACT FROM AUTHOR]

Background: Intraosseous periodontal defects present a particular treatment problem. New bone replacement grafts offer promise for improved results.Methods: The role of a synthetic cell-binding peptide (P-15), combined with anorganic [corrected] bovine-derived hydroxyapatite bone matrix (ABM), was compared to ABM alone in human periodontal osseous defects in a controlled, monitored, multi-center trial. Following appropriate initial preparation procedures, flap surgery with defect and root debridement was performed. Two osseous defects per patient were treated randomly with each procedure after surgical preparation. Appropriate periodontal maintenance schedules were followed, and at 6 to 7 months, re-entry flap surgery was performed for documentation and finalization of treatment.Results: T test and Mann-Whitney U analyses of patient mean values from 33 patients revealed that the combination ABM/P-15 grafts demonstrated significantly better mean defect fill of 2.9 +/- 1.2 mm (72.9%) versus a mean defect fill of 2.2 +/- 1.4 mm (50.67%) for defects treated with ABM (P<0.05). Other hard tissue findings showed similar clinically superior results with the use of ABM/P-15. Relative defect fill results showed 81% positive (50% to 100% defect fill) responses with ABM/P-15 and 67% positive responses with ABM. There were 3.5 times as many optimal results (> or = 90% defect fill) with ABM/P-15 and twice as many failures (minimal response) with ABM. Soft tissue findings showed no significant differences between treatments.Conclusions: These results suggest that the use of the P-15 synthetic cell-binding peptide combined with ABM yields better clinical results than the ABM alone in intrabony periodontal defects. [ABSTRACT FROM AUTHOR]

Background: This study evaluated patients who had been treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded in an absorbable collagen sponge (ACS) in human extraction sites or in sites that required alveolar ridge augmentation. An earlier report on the same patients revealed that after 4 months, implantation of rhBMP-2/ACS was safe, as determined by clinical, radiographic, systemic, and immunological analyses. In this longer-term follow-up, eligible patients were restored with endosseous dental implants in the area treated with rhBMP-2/ACS and bone biopsy samples were taken for histological analysis of the treated human bone tissue. The primary objective was to monitor the long-term safety of patients treated with rhBMP-2/ACS. Another objective was to evaluate the dental implants placed in the sites treated with rhBMP-2. Methods: Patient safety was evaluated by clinical examinations, periapical radiographs, and occurrence of adverse experiences. Dental implants were evaluated by radiographic and clinical examination. All 12 patients have been followed for 3 years. Results: Two years following surgical implantation of rhBMP-2/ACS, no serious or unexpected adverse experiences occurred. The adverse experiences that did occur were mostly benign and compatible with the dental implant surgeries performed in these patients. No adverse experiences were deemed as related to the rhBMP-2/ACS. Furthermore, no safety concerns in the local area of rhBMP-2/ACS placement were noted, based on oral wound examinations. In the 10 patients (6 extraction socket patients and 4 augmentation patients) who received endosseous implants, all implants were clinically stable at all assessments and all 10 patients have been functionally restored. Histological evaluation of the human bone core biopsies revealed normal bone tissue formation identical to the surrounding native bone. Three-year follow-up clinical examinations revealed that all implants had stable marginal bone levels and healthy peri-implant tissues. Conclusions: These 3-year results demonstrate that rhBMP-2/ACS can be used safely in human patients. Human bone biopsies reveal normal bone formation in areas treated with rhBMP-2/ACS. Endosseous implants placed in these areas were all stable with no radiographic or clinical complications. The results from this study suggest that rhBMP-2/ACS (0.43 mg/ml) can be safely used in tooth extraction sites and in local ridge augmentation procedures and that endosseous dental implants placed in bony areas treated with rhBMP-2/ACS are stable and can be functionally restored without complication. [ABSTRACT FROM AUTHOR]

Background: Gingival recession represents a significant concern for patients and a therapeutic problem for clinicians. Several techniques have been proposed to achieve root coverage. The purpose of this randomized clinical trial was to evaluate the effect of a guided tissue regeneration (GTR) procedure in comparison to connective tissue graft (CTG) in the treatment of gingival recession defects.Methods: Twelve patients, each contributing a pair of Miller Class I or II buccal gingival recessions, were treated. In each patient one randomly chosen defect received a poly(lactic acid)-based bioabsorbable membrane, while the paired defect received a CTG. Clinical recordings included oral hygiene standards and gingival health, recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), and keratinized tissue width (KT).Results: Mean RD statistically significantly decreased from 2.5 mm presurgery to 0.5 mm with GTR (81% root coverage), and from 2.5 mm to 0.1 mm with CTG (96% root coverage), at 6 months postsurgery. Prevalence of complete root coverage was 58% for the GTR group and 83% for the CTG group. Mean CAL gain was 2.0 mm for the GTR group and 2.2 mm for the CTG group. No statistically significant differences between treatment groups were observed for changes in RD, RW, PD, CAL, and KT.Conclusions: Treatment of human gingival recession defects by means of either GTR or CTG results in clinically and statistically significant improvement of the soft tissue conditions of the defect when pre- and post-treatment measurements were compared. Although differences between CTG and GTR in mean root coverage and prevalence of complete coverage consistently favored the CTG procedure, the differences in measurements were not statistically significant. [ABSTRACT FROM AUTHOR]

The purpose of the present clinical study was to evaluate the effect of guided tissue regeneration (GTR) in comparison to subpedicle connective tissue graft (SCTG) in the treatment of gingival recession defects. A total of 12 patients, each contributing a pair of Miller's Class I or II buccal gingival recessions, was treated. According to a randomization list, one defect in each patient received a polyglycolide/lactide bioabsorbable membrane, while the paired defect received a SCTG. Treatment effect was evaluated 6 months postsurgery. Clinical recordings included full-mouth and defect-specific oral hygiene standards and gingival health, recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), and keratinized tissue width (KT). Mean RD significantly decreased from 3.1 mm presurgery to 1.5 mm at 6 months postsurgery for the GTR group (48% root coverage), and from 3.0 mm to 0.5 mm for the SCTG group (81% root coverage). RD reduction and root coverage were significantly greater in SCTG group compared to GTR group. Mean CAL gain amounted to 1.7 mm for the GTR group, and 2.3 mm in the SCTG group. No significant differences in PD changes were observed within and between groups. KT increased significantly from presurgery for both treatment groups, however gingival augmentation was significantly greater in the SCTG group compared to GTR group. Results indicate that: 1) treatment of human gingival recession defects by means of both GTR and SCTG procedures results in clinically and statistically significant improvement of the soft tissue conditions of the defect; and 2) treatment outcome was significantly better following SCTG compared to GTR in terms of recession depth reduction, root coverage, and keratinized tissue increase. [ABSTRACT FROM AUTHOR]

The aim of the present study was to clinically and radiographically compare guided tissue regeneration (GTR) therapy with bioabsorbable polyglactin 910 barriers and conventional periodontal surgery in intrabony defects. In 26 patients with advanced periodontitis, 29 teeth exhibiting interproximal intrabony defects were treated; 15 by conventional periodontal surgery (control) and 14 by GTR (test). Before and 12 months after surgery, clinical parameters were assessed and standardized radiographs were taken. On the radiographs the distances from the cemento-enamel junction (CEJ) to the alveolar crest (AC), and the CEJ to the most apical extension of the bony defect (BD) were measured using a computer-assisted analyzing device (LMSRT). Twelve months after surgery, 24 patients with 27 lesions were available for examination. For both methods statistically significant (P < 0.001) probing depth (PD) reduction (mean +/- standard deviation) of -4.49 +/- 1.94 mm (n = 13, test) and -3.22 +/- 1.48 mm (n = 14, control), as well as clinical attachment gain (CAL-V) of 3.41 +/- 1.59 mm (test) and 2.07 +/- 1.10 mm (control), was observed. Radiographic changes of the distance CEJ to AC of -0.95 +/- 1.72 mm (n = 9, test), and -0.98 +/- 1.53 mm (n = 11, control) were not significant. A significant bony fill (distance CEJ-BD) of 1.05 +/- 1.22 mm was observed for the test group (P < 0.01); the 0.68 +/- 2.04 mm bony gain for the control group was not statistically significant. The PD reduction (P < 0.05) and attachment gain (P < 0.01) in the test group was statistically significantly more favorable than in the control group. Twelve months after surgery, statistically more favorable PD reduction and attachment gain was observed using polyglactin 910 barriers than compared to conventional flap surgery. Hence, the use of bioabsorbable barriers for therapy of intrabony defects may be recommended. [ABSTRACT FROM AUTHOR]

Subcutaneous emphysema (SCE) is a possible complication of both nonsurgical and surgical endodontic treatment. A review of the literature pertinent to endodontic intervention and SCE is highlighted, while the causes of and recommendations for the prevention of SCL are provided. A review of the pathways whereby compressed air may travel through potential spaces in the head and neck is also illustrated in an attempt to identify the possibility of morbidity and even mortality should operator induced SCE occur in a patient. [ABSTRACT FROM AUTHOR]

Fluvoxamine and imipramine were compared to placebo in an 8-week double-blind randomized multicentre trial comprising of 148 outpatients between 19 and 57 years of age (mean: 35) with a DSM-III-R diagnosis of Panic Disorder. Mean daily dose at endpoint was: fluvoxamine, 171.4 mg; imipramine 164. 7 mg. The mean number of panic attacks per week at baseline were 10.9, 14.4 and 6.5 for fluvoxamine, imipramine and placebo, respectively. The intent-to-treat analysis of the change from baseline (difference score) of the number of panic attacks at endpoint revealed: a difference of 3.3 attacks (95% Cl: -0.3, 6.8) between fluvoxamine and placebo and a difference of 6.0 attacks (95% Cl: 1.5, 10.5) between imipramine and placebo. Treatment was stopped prematurely in 31 (62%) on fluvoxamine, 16 (33%) on imipramine and 29 (58%) on placebo. The number of patients withdrawing due to intolerance was 13 (26%) for fluvoxamine, I0 (21%) for imipramine and 4 (8%) for placebo. The number of patients withdrawing due to lack of efficacy was I0 (20%) for fluvoxamine, 4 (8%) for imipramine and 12 (24%) for placebo. Overall, this study demonstrated that fluvoxamine was not effective in the treatment of panic disorder but did show a strong effect for imipramine. A chance occurrence of significantly fewer number of panic attacks in the placebo group at baseline may limit the conclusions of this study. [ABSTRACT FROM AUTHOR]

This was a multicenter, randomized, double-blind, parallel trial conducted in outpatients in three countries. Following screening and placebo washout, patients received brofaromine (a combined MAO-A inhibitor/5-HT transport inhibitor) or placebo in a flexible dosing design. Based upon the CAPS, a standardized post-traumatic stress disorder (PTSD) interview, findings from a cohort involving both subchronic and chronic traumatic stress marginally favored brofaromine over placebo; however, not to a statistically significant degree. With a more conservation definition of the syndrome, employing a primary cohort of patients with PTSD of one year or greater duration, brofaromine significantly reduced PTSD symptoms in comparison with placebo. In all analyses a substantial proportion of patients in both drug and placebo groups remained symptomatic throughout. Findings were supported by an analysis of secondary measures. Brofaromine may be of benefit in the therapy of PTSD. [ABSTRACT FROM AUTHOR]

This article focuses on the study of patients with mental retardation. An important aspect of research on mental retardation is the interest in, and attention to, genetic aspects of the subject. Amongst others, this has provided a basis for more rational therapeutic and preventative approaches in a significant number of instances. Of the some 8000 hospitalized mentally retarded patients in the Republic of South Africa in 1982, approximately 5200 individuals were in full-time residential care provided for by central government institutions.

The use of botulinum toxins to decrease spasticity in children with cerebral palsy has become standard of care during the past decade. In 2008 reports of severe adverse events, including death, were reported in children who received injections of these medications. The following discussion focuses on the background of these reports, the response of the U.S. Food and Drug Administration, as well as the safety profile and pharmacokinetics of botulinum toxins. Finally, the authors will offer their perspective on the safe use of botulinum toxins. [Copyright &y& Elsevier]

The article presents an update on heart failure management, focusing on the understanding of peripartum cardiomyopathy (PPCM). It discusses the incidence, risk factors and pathophysiology of PPCM and the biomarkers in heart failure. It offers information on the treatment of the disease and the outcomes of PPCM treatment. It also talks about the risk for PPCM associated with future pregnancy.

This article presents information about a study related to the behavioral dimensions of the de Lange syndrome. The study offers an alternative treatment of self-injurious behavior and outlines a number of non-punishment-oriented treatment techniques. In the initial treatment process, the primary goal is to gain instructional control over the mentally retarded person's behavior. This is achieved by fully tolerating all of the person's inappropriate behavior, while constantly redirecting the person toward developmental tasks which will permit him to explore and profit from sequential learning experiences. The redirecting process is facilitated by the use of ongoing, intensive developmental programming.

Abstract: Despite intensive neurorehabilitation, extensive functional recovery after spinal cord injury is unattainable for most individuals. Optimal recovery will likely depend on activity-based, task-specific training that personalizes the timing of intervention with the severity of injury. Exercise paradigms elicit both beneficial and deleterious biophysical effects after spinal cord injury. Modulating the type, intensity, complexity, and timing of training may minimize risk and induce greater recovery. This review discusses the following: (a) the biological underpinning of training paradigms that promote motor relearning and recovery, and (b) how exercise interacts with cellular cascades after spinal cord injury. Clinical implications are discussed throughout. [Copyright &y& Elsevier]

Abstract: The costs associated with treating spine-related conditions are enormous and are trending upward. Current methods employed to treat inflammatory-mediated pain are targeted at alleviating symptoms, rather than correcting the underlying cause of disease. It is clear that a biochemical basis for inflammatory-mediated intervertebral disk, facet joint, and nerve pain exists. Biologic therapies that address the underlying cause of pain could potentially decrease the costs associated with treating spine pathology. MMPs, IL-1, TNF- α, IL-6, NGF, bradykinin, prostaglandins, and nitric oxide are implicated in much of the catabolic effects seen in the pathogenesis of inflammatory-mediated pain and are good targets for inhibition. The anticatabolic and anabolic effects of TIMPs, BMPs, TGF- β, and IGF-1 are targets already shown to favorably impact disk matrix homeostasis. With rapid advances in biomedical technology, these interventions may be available for clinical use in the near future. [Copyright &y& Elsevier]

Abstract: Cytidine 5′-diphosphocholine (CDP-choline or citicoline) is a highly bioavailable compound with potential benefits for aiding neural repair and increasing acetylcholine levels in the central and peripheral nervous system. As a result, many researchers have investigated the use of CDP-choline for various types of neurological insult or conditions, including stroke, traumatic brain injury, and Alzheimer disease. Despite the fact that the safety of the compound has been verified across multiple international studies, evidence for efficacy remains less clear. This may be attributable, at least in part, to several issues, including a lack of randomized clinical trials, a lack of availability of the compound in the United States, and statistical power issues in reported trials. In addition, the fact that CDP-choline has multiple potential points of therapeutic impact makes it an exciting treatment option in theory but also complicates the analysis of efficacy in the sense that multiple mechanisms and time points must be evaluated. Although some clinical conditions do not appear to benefit from CDP-choline treatment, the majority of findings to date have suggested at least minor benefits of treatment. In this review we will examine the evidence in the published literature pertaining to use of CDP-choline in rehabilitation populations and briefly consider the work yet to be done. [Copyright &y& Elsevier]