Angiogenic biomarkers and healing of living cellular constructs.

The use of intra-oral soft-tissue-engineered devices has demonstrated potential for oral mucosa regeneration. The aim of this study was to investigate the temporal expression of angiogenic biomarkers during wound healing of soft tissue reconstructive procedures comparing living cellular constructs (LCC) with autogenous free gingival grafts. Forty-four human participants bilaterally lacking sufficient zones of attached keratinized gingiva were randomly assigned to soft tissue surgery plus either LCC or autograft. Wound fluid samples were collected at baseline and weeks 1, 2, 3, and 4 post-operatively and analyzed for a panel of angiogenic biomarkers: angiogenin (ANG), angiostatin (ANT), PDGF-BB, VEGF, FGF-2, IL-8, TIMP-1, TIMP-2, GM-CSF, and IP-10. Results demonstrated a significant increase in expression of ANT, PDGF-BB, VEGF, FGF-2, and IL-8 for the LCC group over the autograft group at the early stages of wound repair. Although angiogenic biomarkers were modestly elevated for the LCC group, no clinical correlation with wound healing was found. This human investigation demonstrates that, during early wound-healing events, expression of angiogenic-related biomarkers is up-regulated in sites treated with LCC compared with autogenous free gingival grafts, which may provide a safe and effective alternative for regenerating intra-oral soft tissues (ClinicalTrials.gov number, NCT01134081).

Predictors of outcome for patients with COPD requiring invasive mechanical ventilation.

INTRODUCTION: Accurate outcomes data and predictors of outcomes are fundamental to the effective care of patients with COPD and in guiding them and their families through end-of-life decisions. DESIGN: We conducted a retrospective cohort study of 166 patients using prospectively gathered data in patients with COPD who required mechanical ventilation for acute respiratory failure of diverse etiologies. RESULTS: The in-hospital mortality rate for the entire cohort was 28% but fell to 12% for patients with a COPD exacerbation and without a comorbid illness. Univariate analysis showed a higher mortality rate among those patients who required > 72 h of mechanical ventilation (37% vs 16%; p < 0.01), those without previous episodes of mechanical ventilation (33% vs 11%; p < 0.01), and those with a failed extubation attempt (36% vs 7%; p = 0.0001). With multiple logistical regression, higher acute physiology score measured 6 h after the onset of mechanical ventilation, presence of malignancy, presence of APACHE (acute physiology and chronic health evaluation) II-associated comorbidity, and the need for mechanical ventilation > or = 72 h were independent predictors of poor outcome. CONCLUSIONS: We conclude that among variables available within the first 6 h of mechanical ventilation, the presence of comorbidity and a measure of the severity of the acute illness are predictors of in-hospital mortality among patients with COPD and acute respiratory failure. The occurrence of extubation failure or the need for mechanical ventilation beyond 72 h also portends a worse prognosis.

Weaning from prolonged mechanical ventilation.

The development of weaning failure and need for PMV is multifactorial in origin, involving disorders of pulmonary mechanics and complications associated with critical illness. The underlying disease process is clearly important when discussing mechanisms of ventilator dependence; interventions therefore must be tailored to individual patients. Unfortunately, the main conclusion that can be drawn from the sum of the studies investigating patients on PMV to date is that an evidence-based approach to weaning is not possible and more research needs to be done. New studies need to incorporate severity-of-illness scores and an assessment of principal and comorbid conditions to allow for comparison of the findings from different centers. The best approach to a patient requiring PMV after exclusion of easily treatable conditions is not known. The literature regarding both acute and chronic cases suggests that a systematic approach to weaning involving the participation of multiple caregivers, including nurses, physicians, and respiratory, physical, and speech therapists facilitates liberation from MV. Although a gradual decrement in ventilator support would seem prudent, Scheinhorn et al have begun to identify a subpopulation of patients who can tolerate an acceleration of the weaning process. Given the known complications associated with MV, it is crucial that further research be performed to identify patients as soon as they are capable of breathing spontaneously. The literature demonstrates through multiple studies that satisfactory patient outcomes are attainable and can be achieved at LTAC facilities in a more cost-effective manner than in an ICU setting. The trend toward the concentration of patients into specialized regional weaning centers should facilitate the research process and continue to improve outcomes in this population.

Relationship between crevicular aspartate aminotransferase levels and periodontal disease progression.

BACKGROUND: Aspartate aminotransferase (AST), an enzyme released from necrotic cells, has been identified in gingival crevicular fluid (GCF), and elevated levels are associated with periodontal tissue destruction. The aim of this study was to examine the relationship between elevated GCF levels of AST and periodontal disease progression. METHODS: Over a 12-month period, 8 to 10 interproximal sites in 41 periodontitis subjects (PS) and 15 healthy subjects (HS) were monitored. Clinical measurements included relative attachment level (RAL), probing depth, and bleeding on probing (BOP). Semiquantitative levels of GCF AST (< 800 microIU, > or = 800 microIU, and > or = 1,200 microIU) were determined using a chairside assay. At the 6- and 12-month visits, scaling and root planing and prophylaxis were performed in the PS and HS, respectively. Sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) were calculated for 2 diagnostic criteria (AST > or = 800 microIU, AST > or = 1,200 microIU) utilizing 4 thresholds of disease progression as determined by 2 methods (absolute change in relative attachment level and cumulative sum [CUSUM]). RESULTS: The percentage of sites exhibiting AST > or = 800 microIU, AST > or = 1,200 microIU, and BOP in the PS was significantly (P<0.02) lower at 6 and 12 months compared to baseline. The use of crevicular AST activity to monitor periodontal disease progression was associated with many false-positive results. Overall, low specificities, PPV, and odds ratios were demonstrated by the assay when using 2 diagnostic criteria and 4 thresholds of disease progression. The high NPV suggest that a negative AST test result was indicative of a periodontally stable site. CONCLUSIONS: These results demonstrate that elevated levels of AST were present at sites that did not subsequently exhibit disease progression. The high prevalence of AST-positive sites due to gingival inflammation diminished the test's ability to discriminate between progressive and stable, but inflamed, sites.

Periodontal regeneration with an autogenous bone-Bio-Oss composite graft and a Bio-Gide membrane.

This study evaluated the clinical, radiographic, and histologic response to the composite use of Bio-Oss porous bone mineral and autogenous bone in combination with a Bio-Gide bilayer collagen membrane to achieve regeneration when treating human periodontal bone defects. Preoperative recordings for four treatment areas included radiographs, clinical probing depths, and attachment levels; these recordings were repeated at 9 months. Histologic evaluation revealed new cementum with inserting collagen fibers and new bone formation on the surface of both types of graft materials. This grafting combination not only compared favorably with the previous use of Bio-Oss and Bio-Gide, but exceeded that result with almost complete periodontal regeneration. This human histologic study demonstrates that autogenous bone in combination with porous bone mineral matrix, together with the Bio-Gide collagen membrane, has the capacity to stimulate substantial new bone and cementum formation with Sharpey's fiber attachment.

Correlation of peri-implant health and aspartate aminotransferase levels: a cross-sectional clinical study.

At present, there are no diagnostic tools that permit early detection of peri-implantitis. The purpose of this cross-sectional study was to evaluate the correlation of aspartate aminotransferase (AST) levels with traditional periodontal clinical parameters around dental implants, since AST has been associated with destruction of cardiac, hepatic, and periodontal tissues. Twenty healthy volunteers with 59 implants were recruited from the Harvard School of Dental Medicine clinics. Clinical parameters evaluated included: AST level, probing depth (mm), Gingival Index (0, 1, 2, or 3), and bleeding on probing (0 or 1). Utilizing the site or implant as the unit of measure, the authors found a statistically significant association of increased AST activity with positive bleeding on probing, increased probing depth, and increased Gingival Index. No statistical correlations were found between clinical indices and increased AST levels when the results were examined on an individual patient basis. This cross-sectional study was able to demonstrate a statistical correlation between diseased clinical periodontal parameters and elevated AST levels.

Effect of unplanned extubation on outcome of mechanical ventilation.

Unplanned extubation is a major complication of translaryngeal intubation, but its impact on mortality, duration of mechanical ventilation (MV), length of intensive care unit (ICU) and hospital stay, and need for ongoing hospital care has not been adequately defined. We performed a case-control study in a tertiary-care medical ICU, comparing 75 patients with unplanned extubation and 150 controls matched for Acute Physiology and Chronic Health Evaluation II score, presence of comorbid conditions, age, indication for MV, and sex. Forty-two (56%) patients required reintubation after unplanned extubation (74% immediately, 86% within 12 h). Thirty-three (44%) unplanned extubations occurred during weaning trials, and 30% of these patients needed reintubation (failed unplanned extubation). In contrast, 76% of patients with unplanned extubation occurring during ventilatory support required reintubation. Although mortality was similar to that of controls (failed unplanned extubation 40%, versus control 31%, p > 0.2), patients with failed unplanned extubation had a significantly longer duration of MV (19 versus 11 d, p < 0.01), longer stay in the ICU (21 versus 14 d, p < 0.05), and longer hospital stay (30 versus 21 d, p < 0.01), and survivors were more likely to require chronic care (64% versus 24%, p < 0.001). Successfully tolerated unplanned extubation was associated with a reduction in time from beginning of weaning to extubation (0.9 versus 2.0 d, p = 0.06), but with no difference in overall duration of MV, mortality, discharge location, ICU, or hospital stay as compared with these measures for controls. We conclude that unplanned extubation is not associated with increased mortality when compared with that of matched controls, although it does result in prolonged MV, longer ICU and hospital stay, and increased need for chronic care. These effects are due exclusively to patients who fail to tolerate unplanned extubation. Although successfully tolerated unplanned extubation decreased the duration of weaning trials, it had no other measurable beneficial impact on outcome.

Treatment of Class II furcations with autogenous bone grafts and e-PTFE membranes.

This article reports a successful clinical regimen of treatment for the Class II furcation defect. Twenty-eight patients with molar teeth demonstrating Class II furcations were treated with regenerative therapy with the goal of regenerating lost interradicular periodontium. The treatment selected included scaling and root planing, surgical flap design that would enable the flap to completely cover the surgical site, complete enucleation of granulation tissue, tetracycline root conditioning, a particulate autogenous bone graft, and an expanded polytetrafluoroethylene (e-PTFE) membrane. Of the twenty-eight consecutive patients treated, twenty-five demonstrated no postoperative clinical evidence of furcation invasion, for a success rate of 89%. Eleven sites were reopened 8 to 9 months postsurgical and presented complete furcation fill with a hard, bone-like tissue. Three teeth were judged to be failures because clinical assessment revealed persistent furcation invasion. The absence of histologic evidence precludes the presumption that complete periodontal regeneration occurred.

Clinical and histologic evaluation of human gingival recession treated with a subepithelial connective tissue graft and enamel matrix derivative (Emdogain): a case report.

A mandibular canine with significant gingival recession was selected for a pilot study to measure the attachment modalities resulting from mucogingival surgery. The tooth had 6 mm of recession as measured from the cementoenamel junction to the gingival margin, minimal pocketing, and no keratinized gingiva. The treatment regimen consisted of a subepithelial connective tissue graft (SCTG) plus Emdogain applied to the root surface. The tooth was extracted en bloc 6 months after surgery and processed histologically in a buccolingual plane. The tooth demonstrated a 2-mm gain of attachment and a 3-mm gain in keratinized tissue. The histologic study evidenced the migration of the junctional epithelium 1.2 mm apical to the sulcus. New cementum, evidence of newly formed woven bone, and connective tissue fibers anchored in the new cementum were evident.

A retrospective study of dental implants in diabetic patients.

The efficacious placement of dental implants in diabetic patients remains controversial. Definitive guidelines with objective criteria, including the type of diabetes, age of onset, and level of long-term control, have not been determined. In addition, few relevant literature citations assess the survival rate of implants in diabetic patients. Therefore, it is the purpose of this study to assess the success and survival rates of dental implants in diabetic patients. In this retrospective analysis, 215 implants placed in 40 patients at 2 clinical centers were evaluated. Chart reviews and interviews provided medical and implant data. From the analysis, 31 failures occurred, for an overall success rate of 85.6%. Of these failures, 24 occurred within the first year of functional loading. The mean time of functional load was 4.05 +/- 2.6 years. When the success rate was analyzed by implant location, success rates for the maxilla and mandible were 85.5% and 85.7%, respectively. For the anterior and posterior regions, success rates were 83.5% and 85.6%, respectively. The lifetable analysis revealed a cumulative success rate of 85.7% after 6.5 years of function. Based on the data, the survival rate of dental implants in controlled diabetic patients is lower than that documented for the general population, but there is still a reasonable success rate. The increase in failure rate occurs during the first year following prosthetic loading.

Human histologic evaluation of bioactive ceramic in the treatment of periodontal osseous defects.

This study examined the healing of intrabony defects around 5 teeth treated with bioactive glass ceramic (PerioGlas). Healing was evaluated by clinical measurements, radiographic observation, and histologic analysis. The protocol included a presurgical phase of scaling and root planing therapy, with measurements obtained immediately prior to the surgical procedures and after 6 months of healing. Following therapy there was a mean of 2.7 mm of probing depth reduction, 2.2 mm of clinical attachment gain, and 0.5 mm of recession. The histologic analysis revealed healing by a long junctional epithelium with minimal new connective tissue attachment to the teeth, except in one case where the intrabony region demonstrated new cementum formation and new connective tissue attachment. Graft particles were found to be biocompatible, as evidenced by being embedded in a stroma of dense connective tissue with minimal inflammatory infiltrate. There was minimal new bone formation limited to the most apical borders of the defects. No signs of periodontal regeneration as defined by new cementum, periodontal ligament, and bone formation on a previously diseased root surface were observed. Although the clinical results are encouraging and radiographs evidenced radiopacities within the defects, histologic analysis revealed that as a periodontal grafting material, bioactive glass ceramic has only limited regenerative properties.

The effect of insulin therapy on osseointegration in a diabetic rat model.

As patients become edentulous, dental implants have been one treatment alternative. Although studies indicate that dental implants inserted in healthy patients have been successful, their placement in the diabetic patient remains controversial. The purpose of this study utilizing histometric parameters compares the course of osseous healing around endosseous implants in normal non-diabetic and insulin controlled diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin. Blood glucose was monitored by the glucose-oxidase method and controlled with daily insulin injections. Sterile custom fabricated commercially pure solid cylinder titanium implants, with a titanium plasma-sprayed surface were placed in the femora of each animal. The results indicate that insulin therapy was able to upregulate the formation of bone around implants inserted in the streptozotocin-induced diabetic rat model. However, histometric parameters utilized indicated that although the total quantity of bone formation was greater in the insulin controlled group, there was significantly less bone-to-implant contact in the insulin controlled diabetic group as compared to normal non-diabetic controls.

Wound healing around endosseous implants in experimental diabetes.

Wound healing has been shown to be altered in diabetes mellitus. The aim of this study was to identify the effects of streptozotocin-induced diabetes on osseointegration. Diabetes was induced in 40-day-old rats by intraperitoneal injection of 70 mg per kg streptozotocin. At 14 days postinjection, implants were placed in the femora of 10 diabetic and 10 age-matched normal rats. Animals were sacrificed at 28 and 56 days following implantation. Histometric results indicated that the quantity of bone formation was similar for diabetic and control animals (P > .05). However, less bone-implant contact was observed for diabetic compared to control animals at both 28 and 56 days (P < .0001). This study demonstrates that the process of osseointegration is affected by streptozotocin-induced diabetes.

Clinical, radiographic, and histologic evaluation of human periodontal defects treated with Bio-Oss and Bio-Gide.

This study evaluated the clinical, radiographic, and histologic response to Bio-Oss porous bone mineral when used alone or in combination with Bio-Gide bilayer collagen membrane in human periodontal defects. Four intrabony periodontal defects were treated: two received Bio-Oss alone and two were treated with a combination of Bio-Oss and Bio-Gide. Radiographs, clinical probing depths and attachment levels were obtained preoperatively and 6 to 9 months postoperative, and teeth and surrounding tissues were biopsied. Both treatments significantly improved clinical probing depths and attachment levels, and the radiographic appearance suggested osseous fill. Histologic evaluation revealed that both treatments produced new cementum with inserting collagen fibers and new bone formation on the surface of the graft particles; this regenerative effect was more pronounced using the Bio-Oss/Bio-Gide combination, which resulted in 7 mm of new cementum and periodontal ligament and extensive new bone incorporating the graft. The membrane was intact at 7 months and partially degraded by 9 months after treatment. This human histologic study demonstrates that the porous bone mineral matrix used has the capacity to stimulate substantial new bone and cementum formation and that this capacity is further increased when the graft is used with a slowly resorbing collagen membrane.

A new animal model for maxillary sinus floor augmentation: evaluation parameters.

This study describes a novel animal model of the maxillary sinus floor augmentation procedure used to assess bone formation during 12 weeks in response to a recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) sinus implant. A buffer-ACS implant was used as a control. Animal response was monitored using computerized tomography and physical, hematologic, gross pathologic, and histologic evaluations. The rhBMP-2/ACS implants maintained a relatively constant size postsurgery and showed a time-dependent increase in mineralization. The buffer/ACS control implants failed to mineralize and were resorbed by 4 weeks. The model served effectively and without complication. Results indicate rhBMP-2/ACS implants deserve consideration as alternatives to traditional grafting procedures.

Periodontal, implant, and prosthetic treatment for advanced periodontal disease.

This article reports a case that involved a challenge in multidisciplinary decision making. A patient presented with severe periodontal disease and the need for prosthetic rehabilitation for purposes of tooth replacement and the stabilization of periodontally compromised teeth. The initial diagnosis revealed that the treatment regimen would require periodontic, endodontic, and orthodontic treatment, as well as dental implants. This case report demonstrates teamwork and a sequential approach to a complex case in a postgraduate clinical setting.

Comparison of manual and automated probing in an untreated periodontitis population.

Diagnosis of periodontal disease progression involves recording two probing attachment level measurements over an adequate time interval. A diagnostic instrument which exhibits less measurement variability allows for increased sensitivity and earlier disease detection. Traditionally, a manual probe with an occlusal stent of the cementoenamel junction (CEJ) as a reference landmark has been the method of choice. Automated probes that use an occlusal disk as the reference landmark have been developed as an alternative means of measure. The aim of this study was to compare the variability of these two probing methods. Four hundred eleven (411) interproximal sites in 46 untreated periodontitis patients were monitored by a single examiner over a 6-month period. Each site was measured on a monthly basis, first with an automated probe (AP) followed by a manual probe (MP) in combination with a custom-fabricated acrylic stent. Measurement variability of the two probing methods was also compared over a 7-day interval. The AP measurements were significantly more variable than the MP measurements (P < 0.001) when considering the variability between two passes at the same visit. Over the 6-month period, the MP measurements demonstrated significantly more variability than the AP measurements (P < 0.001). It was also noted that MP measurements exhibited more variability at sites with frequent bleeding during the 6 months of the study (P = 0.006). The results of this study demonstrate that AP may have less variability of attachment level measurements over a 6-month period and may be less influenced by local inflammatory changes. However, future comparison studies should include multiple examiners to reduce examiner bias and should alternate the probing method to reduce bias created by local tissue changes from multiple probings.