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Subgingival plaque samples were obtained from 162 sites in 27 adult periodontitis patients and 162 sites in 27 healthy patients using a standardized lavage technique. The distribution of 10 different microbial morphotypes was determined by darkfield microscopy. The lavage technique selectively samples the loosely adherent plaque at the base of the periodontal pocket and not the tooth-associated, adherent plaque. This standardized technique permits quantitative comparisons of numerical density of morphotype composition at different sites, in addition to qualitative comparisons or relative proportions. There was a significant positive association between the numerical density of each morphotype within the non-adherent plaque and the number of sites at which the organism was detected in both healthy and diseased subjects. A previously undescribed darkfield morphotype, has been detected with this method. This morphotype, a small motile coccobacillus (S-MO-CB) has been found to be the numerically dominant species in both health and disease. This morphotype has been recovered in pure culture following passage through a 0.4 μ filter and includes organisms of the Wollinella and Campylobacter genus. Non-motile organisms comprised less than 1-2% of the sample from healthy and diseased sites. Motile forms, such as spirochetes, had a high frequency of detection in healthy individuals. Analysis of pooled plaque samples revealed that the prevalence of cocci and fusiforms was significantly elevated in patients with healthy periodontium, as compared to patients with adult periodontitis. In adult periodontitis patients, the frequency of occurrence of medium spirochetes, filaments and small nonmotile rods was significantly elevated in pooled plaque. Analysis of individual sites indicated that the proportion and numerical density of most morphotypes within the non-adherent plaque were not significantly different in disease as compared to health. Disease is characterized by an increased % of small spirochetes and fusiforms at each site. At diseased sites which harbor small spirochetes, the numerical density is elevated four-fold, as compared to healthy sites which have small spirochetes. The numerical density of other morphotypes is not significantly different comparing healthy sites to diseased sites. Thus, the increase in the % of small spirochetes in disease in due to a site-localized four-fold increase in numerical density within the non-adherent plaque. [ABSTRACT FROM AUTHOR]

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The four principal metabolites of cyclooxygenase (CO) were examined during the progression of experimental periodontitis in the rhesus monkey Macaca mulatta. Thirty-two monkeys were divided in four disease-matched groups. Three groups were treated with flurbiprofen. a potent CO inhibitor, at either 0.027, 0.27 or 7.1 mg/kg/day delivered systemically by a subcutaneously-implanted osmotic mini-pump. We have previously described the findings indicating that flurbiprofen treatment significantly retarded clinical attachment loss (ALOSS), redness and radiographic bone loss (BLOSS). This investigation focuses on the changes in CO metabolites which occur during disease progression of ligature-induced periodontitis and on the dose-response relationship of flurbiprofen, as it relates to disease inhibition and the suppression of ARA metabolites within the crevicular fluid (CF). In untreated animals there was a statistically significant 3-fold increase in CF levels of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) at 3 months, as compared to baseline, which positively correlated with increases in redness, bleeding, ALOSS and BLOSS. CF-PGE2 and TxB2 levels reached a 6-fold peak at 6 months and returned to baseline by 12 months. Flurbiprofen (Fb) prevented the 3-month rise in TxB2, but did not affect the increase in PGE2. At 6 months, Fb administration caused a dose- dependent inhibition of both PGE2 and TxB2. Probit analysis of the dose- response data revealed that the concentration of Fb which caused a 50% inhibition of CF-TxB2, level (the IC50 value for TxB2, synthesis) was approximately two logs lower than the IC50 value for PGE2 synthesis, i.e. TxA2-IC50 = 0.013 vs. PGE2-IC50= 1.35 mg flurbiprofen/kg/d. The slopes of the PGE2 and TxB2 inhibition curves were identical, consistent with a similar mechanism or singular enzyme for the site of action of Fb inhibition of CO activity. However, the kinetics and sensitivity of Fb inhibition were significantly different for the CO activity responsible for TxB2 and PGE2 synthesis, perhaps due to different compartmentalization of CO within different cell types. [ABSTRACT FROM AUTHOR]

The effect of the nonsteroidal anti-inflammatory drug flurbiprofen has been studied in the ligature-induced and spontaneous peridontitis model in the rehsus monkey, Macaca mulatta. Twenty -four adult monkeys with incipient peridontits were divided into three disease-matched groups. Two groups received flurbioprofen at dosages of either 0.27 mg/kg/d or 7.1 mg/kg/d delivered systimatically via osmotci minipump. A split-mouth approach was used, placing lignatures on one side and monitoring the progression of periodontitis at regular interval for 6 months. Clinical measurements included standardized radiographs, Ramfjord attachment level determination and assessments of redness, edema and bleeding on probing. There was a statistically significant inhibition of attachment loss (p<0.05), gingival redness (p<0.05) and bleeding on probing (p<0.05) in ligature-induced and spontaneous peridontits in the flurbiprofen-treated animals at 6 months. Eight of 8 ligated control monkeys losts attachment (mean loss of 1.06 mm/site). Only 3 of 15 flurbiprofen-treated ligated monkeys lost any significant attachment with an overall mean loss of 0.34 mm/site, which was significantly less than the control loss of 1.06 mm/site at p=4.46 × 10-3. The odds of a control ligated monkey undergoing attachment loss in 6 months are elevated 29.3-fold as compared to the flurbiprofen-treated cohort monkey group. Flurbiprofen treatment also significantly inhibited spontaneous attachment loss for 6 months as compared to control monkeys at p<0.005 . These data provide further evidence for the central role of cylcooxygenase product in the progression of periodontal disease. The ability of flurbiprofen to inhibit periodontal attachment loss, even in the presence of loss plaque accumulation, has significant implications for the potential use of flurbiprofen as an adjunctive periodontal therapeutic modality. [ABSTRACT FROM AUTHOR]

Longitudinal data were collected over a period of at least 18 months and up to 3 years on 41 adult periodontitis patients (AAP Type III and IV). Rainfjord attachment level measurements and sampling of crevicular fluid (CP) at each tooth were repeated every 3 months. A mean full mouth CF prostaglandin E2 (MCF-PGE) value was determined for each patient at each visit. The three-mouth monitoring was continued until a single site demonstrated a statistically and clinically significant attachment loss (ALOSS) episode. Results indicated that in ALOSS patients the MCF-PGE was significantly elevated at the ALOSS visit as compared to previous levels. Furthermore, the sites which had the ALOSS had elevated levels as compared to the contralateral no ALOSS control sites (305.6±56.5 vs. 65.7 ± 6.89 ng/ml, mean±SEM). One month following treatment the CF-PGE level dropped to 16.9± 3.4 ng/ml at the ALOSS sites. Since the MCF-PGE level increases preceding the attachment loss episode, reaches a maximum at the sites which actually undergo ALOSS, and subsides following treatment, the possibility of using the MCF-PGE level to predict an oncoming future ALOSS episode was examined. The ALOSS patients had a MCF-PGE level of 113.4±9.0 ng/ml 6 months prior to the ALOSS episode, which was significantly higher than the no ALOSS patients' MCF-PGE level of 50.1±7.1. Analysis of MCF-PGE levels as a screening test indicate that this measurement has a high degree of sensitivity, specificity, and a predictive value of 0.92 0.95. Thus, this method has significant merit as a diagnostic tool to determine if a patient is in a state of remission or about to undergo an attachment loss episode. [ABSTRACT FROM AUTHOR]

The measurement of crevicular fluid PGF (CF-PGE) as an indicator of periodontal disease status was investigated. The association between CF-PGE levels and the PGE content of the adjacent periodontal tissues was found to be highly significant (P = 5.3 × 10). The high correlation (r = 0.925) between the log CF-PGE level and the tissue PGE concentration indicates that CF levels can be used to reliably predict tissue levels. The CF-PGE measurements at each periodontal site were found to be highly reproducible. Samples from adult and juvenile periodontitis patients demonstrated that the mean CF-PGE levels were correlated with disease severity, as determined by mean attachment loss. The mean CF-PGE level in juvenile periodontitis patients was almost three-fold higher than that present in adult periodontitis (144.0 ± 28.0 ng/ml vs 57.5± 8.7 ng/ml, mean±S.E., significant at P = 0.002). The use of CF-PGE concentrations as an indicator of disease activity (i.e. longitudinal attachment loss) cannot be demonstrated by this cross-sectional study. However, the CF-PGE measurement has been demonstrated to be a non-invasive, sensitive, reproducible, and reliable reflection of tissue levels of PGE2. The association of increasing levels of CF-PGE with increased severity and aggressiveness of disease is consistent with PGE as an inflammatory mediator of tissue destruction. [ABSTRACT FROM AUTHOR]

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species., Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection., Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis., Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents., Competing Interests: P.B.B.—Speaker’s Bureau: bioMérieux. C.M.B.—Speaker’s Bureau: Merck Pharmaceuticals. Grant Funding: ALK Abello. S.T.K.—Speaker’s Bureau: Melinta Therapeutics. J.A.J.—Speaker’s Bureau: bioMérieux. All other authors report no potential conflicts of interest.

Upper limb overuse injuries are common in manual wheelchair users with spinal cord injury. Patient-specific in silico models enhance experimental biomechanical analyses by estimating in vivo shoulder muscle and joint contact forces. Current models exclude deep shoulder muscles that have important roles in wheelchair propulsion. Freely accessible patient-specific models have not been generated for persons with tetraplegia, who have a greater risk for shoulder pain and injury. The objectives of this work were to (i) construct a freely accessible, in silico, musculoskeletal model capable of generating patient-specific dynamic simulations of wheelchair propulsion and (ii) establish proof-of-concept with data obtained from an individual with tetraplegia. Constructed with OpenSim, the model features muscles excluded in existing models. Shoulder muscle forces and activations were estimated via inverse dynamics. Mean absolute error of estimated muscle activations and fine-wire electromyography (EMG) recordings was computed. Mean muscle activation for five consecutive stroke cycles demonstrated good correlation (0.15-0.17) with fine-wire EMG. These findings, comparable to other studies, suggest that the model is capable of estimating shoulder muscle forces during wheelchair propulsion. The additional muscles may provide a greater understanding of shoulder muscle contribution to wheelchair propulsion. The model may ultimately serve as a powerful clinical tool. Graphical abstract ᅟ.

Background: the development of an objective and comprehensive drug-based index of physical function for older adults has the potential to more accurately predict fall risk., Design: the index was developed using 862 adults (ages 57-85) from the National Social Life, Health, and Aging Project (NSHAP) Wave 1 study. The index was evaluated in 70 adults (ages 51-88) from a rehabilitation study of dizziness and balance., Methods: the prevalence among 601 drugs for 1,694 side effects was used with fall history to determine the magnitude of each side effect's contribution towards physical function. This information was used to calculate a Medication-based Index of Physical function (MedIP) score for each individual based on his or her medication profile. The MedIP was compared to the timed up and go (TUG) test as well as drug counts using receiver operating characteristic (ROC) analysis. The associations between various indices of physical function and MedIP were calculated., Results: within the NSHAP data set, the MedIP was better than drug counts or TUG at predicting falls based on ROC analysis. Using scores above and below the cutpoint, the MedIP was a significant predictor of falls (OR = 2.61 [95% CI 1.83, 3.64]; P < 0.001). Using an external data set, it was shown that the MedIP was significantly correlated with fall number (P = 0.044), composite physical function (P = 0.026) and preferred gait speed (P = 0.043)., Conclusion: the MedIP has the potential to become a useful tool in the healthcare and fall prevention of older individuals., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: Obese, type two diabetics are at an increased risk for fracturing their limb bones in comparison to the general population. Phytoestrogens like as the soy isoflavone genistein have been shown to protect against bone loss. In this study, we tested the effects of genistein treatment on femurs of ob/ob mice, a model for obesity and type two diabetes mellitus., Methods: Twenty six-week-old female mice were divided into obese (ob/ob) control, obese genistein-treated, lean (ob/+) control, and lean genistein-treated groups (n = 5 each). Treatment with genistein consisted of 600 mg genistein/kg diet. Control mice were given standard rodent chow. At the end of a four-week treatment period, bone histomorphometric and three-point bending properties were compared among groups., Results: Obese mice had larger bone areas (B.Ar.; P < 0.05) and total areas (Tt.Ar.; P < 0.05), but similar bone volume (B.Ar./Tt.Ar.; P > 0.05) of the proximal femoral epiphysis in comparison to lean mice. Treatment with genistein decreased Tt.Ar. and femur length, and increased ultimate force required to fracture the femur and the maximum deformation to failure (P < 0.05)., Conclusions: Genistein improves resistance to fracture from bending loads.

Background: The Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1 to 4 trials compared rivaroxaban 10 mg daily with commonly used doses of enoxaparin and demonstrated similar rates of VTE and bleeding., Objective: To evaluate bleeding events between patients who received enoxaparin or rivaroxaban for prevention of venous thromboembolism (VTE) following total hip arthroplasty (THA) or total knee arthroplasty (TKA)., Methods: Retrospective cohort that compared patients undergoing THA and TKA who received enoxaparin (enoxaparin) with those who received rivaroxaban (rivaroxaban) and also with those who received enoxaparin in the RECORD 1 to 4 trials (enoxaparin RECORD). The primary outcome was any postoperative bleeding, defined as a composite of major and clinically relevant nonmajor bleeding based on the definitions in the RECORD 1 to 4 trials., Results: There was a lower rate of any postoperative bleeding (2.2% vs 6.8%, P = 0.004) in patients who received enoxaparin compared with rivaroxaban, and bleeding rates between the enoxaparin group and the enoxaparin RECORD groups were similar (2.2% vs 2.5%, P = 0.085). Major bleeding in the enoxaparin group (0.2%) was not significantly different from that in the rivaroxaban group (1.4%, P = 0.12) or the RECORD group (0.2%, P = 0.93). Clinically relevant nonmajor bleeding was also lower in the enoxaparin group compared with the rivaroxaban group (2.0% vs 5.5%, P = 0.012)., Conclusions: The use of enoxaparin for VTE prophylaxis following THA and TKA was associated with a lower rate of the primary outcome (any postoperative bleeding) compared with the use of rivaroxaban in a similar cohort of patients., (© The Author(s) 2016.)

Study Objective: Although data from the Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1-4 trials have shown a similar postoperative bleeding risk between rivaroxban and enoxaparin in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), anecdotal observations from local institutions have suggested that postoperative bleeding rates seemed higher in patients who received rivaroxaban than those reported in the RECORD trials. Thus, the objective of this pilot study was to assess postoperative bleeding events observed in clinical practice in patients receiving rivaroxaban after undergoing THA and TKA and to compare their results with those published in the RECORD trials., Design: Retrospective cohort study with a comparator group of patients from the RECORD 1-4 trials., Setting: Two institutions within a regional health care system., Patients: Four hundred forty adults who received at least one dose of rivaroxaban 10 mg daily after undergoing THA or TKA in the two institutions between August 2011 and October 2013 (cohort group), and 6183 patients who received rivaroxaban in the RECORD 1-4 trials (comparator group)., Measurements and Main Results: Postoperative bleeding was assessed in the cohort patients versus the patients in the RECORD trials. The primary outcome, occurrence of any postoperative bleeding, was a composite of major and clinically relevant nonmajor bleeding as defined in the RECORD trials. Any postoperative bleeding occurred in 6.8% of the cohort patients versus 3.2% of the RECORD trial patients (p<0.0001); 1.4% of the cohort patients versus 0.38% of the RECORD trial patients suffered a major bleed (p=0.013). Within defined major bleeding, bleeding leading to reoperation and clinically overt extrasurgical site bleeding resulting in either a hemoglobin level decrease of at least 2 g/dl or transfusion of 2 units or greater of packed red blood cells were reported in 0.68% versus 0.19% (p=0.073) and 0.68% versus 0.13% (p=0.032), respectively, of the cohort patients versus the RECORD trial patients., Conclusion: Overall, any postoperative bleeding in the cohort patients occurred significantly more frequently than that observed in the RECORD trial patients. The major bleeding rate was also significantly higher in the cohort patients, influenced by higher rates of bleeding leading to reoperation and clinically overt extrasurgical site bleeding resulting in either a hemoglobin decrease of at least 2 g/dl or transfusion of two units or greater of packed red blood cells. These findings from our pilot study are thought provoking and, thus, invite further investigation., (© 2015 Pharmacotherapy Publications, Inc.)

Background: Caffeine is added to dietary supplements to increase energy and suppress appetite. Many people take dietary supplements for weight loss. Patients may be unaware that supplements can contain caffeine, even if caffeine is not listed as an ingredient. Commonly used herbal dietary supplement ingredients, such as guarana, are natural sources of caffeine., Objective: To describe a case of possible caffeine-induced seizure in a patient taking an over-the-counter weight loss supplement., Case Report: A previously healthy 38-year-old female experienced blurring of vision and a new onset grand mal seizure. The patient had a two-month history of taking the dietary supplement, Zantrex - 3™. Zantrex - 3™ is advertised as a weight loss supplement which may provide rapid weight loss and extreme energy in one "power packed pill.", Conclusions/summary: After discontinuation of Zantrex - 3™, the patient experienced no further seizure activity. Outpatient follow up at 2 and 6 weeks was noncontributory with follow up MRI and EEG both within normal limits.

Many dietary supplements being promoted for weight loss contain caffeine- or ephedra-related alkaloids to increase energy and suppress appetite. People may be unaware that supplements can contain caffeine, even if caffeine is not listed as an ingredient. Commonly used herbal dietary supplement ingredients, such as guarana, are natural sources of caffeine. Additions of these natural sources of caffeine to dietary supplements have increased in recent years. We describe a case of possible caffeine-induced seizure in a patient taking an over-the-counter weight loss supplement. A previously healthy 38-year-old female experienced blurring of vision and a new onset grand mal seizure. The patient had a 2-month history of taking the dietary supplement, Zantrex-3™. Zantrex-3™ is advertised as a weight loss supplement, which may provide rapid weight loss and extreme energy in one "power packed pill." Zantrex-3™ is a proprietary blend containing niacin, caffeine, and various herbs. After presenting to the hospital emergency room, the patient's chemistry panel, with the exception of potassium (2.9 mEq/L), was within normal limits. An electroencephalogram (EEG) was unremarkable. The magnetic resonance imaging (MRI) showed possible atrophy in the right frontal lobe. Findings from follow-up MRI and EEG ordered as an outpatient were within normal limits. After discontinuation of Zantrex-3™, the patient has experienced no further seizure activity.

Objective: To report a case of deep vein thrombosis (DVT) with symptomatic pulmonary embolism (PE) possibly associated with the use of coltsfoot, kava, or blue vervain., Case Summary: A 27-year-old white male presented with leg pain and swelling, tachycardia, and pleuritic chest pain. He had no significant medical history. A medication history revealed extensive herbal medication use including: coltsfoot, passionflower, red poppy flower petals, wild lettuce, blue lily flowers, wild dagga flowers, Diviners Three Burning Blend® (comprised of salvia divinorum, blue lily, and wild dagga), kava-kava, St. John's Wort, blue vervain, and Dreamer's Blend® (comprised of Calea zacatechichi, vervain, Entada rheedii, wild lettuce, and Eschscholzia californica). Lower extremity Doppler ultrasound and computed topography (CT) of the chest revealed DVT and PE. A hypercoagulable work-up was negative. The patient was treated with enoxaparin and warfarin and was discharged home., Discussion: While no distinct agent can be identified as a sole cause of this venous thromboembolic event, coltsfoot could potentially affect coagulation through its effect on vascular endothelial cells as they regulate nitric oxide. Nitric oxide is a known mediator of platelet activity and coagulation, particularly in the pulmonary vasculature. Kava and vervain have estrogenic properties., Conclusions: Of the medications consumed by this self-proclaimed "herbalist," coltsfoot is a potential cause of venous thromboembolic disease (VTE).

The unsuccessful treatment of dermatophytosis with griseofulvin is common. The mechanism is not known but may involve infection with a griseofulvin-resistant dermatophyte. The mean minimal inhibitory concentration (MIC) value of griseofulvin for Trichophyton rubrum isolates obtained from griseofulvin unresponsive patients was substantially larger than the mean MIC value for responsive control isolates. This difference indicates that therapeutic failure does correlate with the relative in vitro resistance. An MIC of 3.0 microgram/mL or greater was determined to indicate relative griseofulvin resistance. We conclude that the MIC determination for griseofulvin can be used to determine the appropriateness of griseofulvin therapy.

Terminal deoxynucleotidyl transferase (TdT) is a marker for the diagnosis of acute lymphoblastic leukemia. To determine its value as an indicator of bone marrow remission or impending relapse, serial remission marrows (less than 5% blasts) from 49 patients who had acute lymphoblastic leukemia were examined for TdT by immunofluorescence over the period of a year. Thirty-eight patients (78%) had less than 1% TdT-positive cells. Eleven patients (22%) had slightly elevated levels of TdT (2%-7%) at some time during the study. of these eleven, only two had relapses; however, neither patient had greater than 1% TdT-positive cells within the three months before the relapse. Therefore, it appears that the presence of slightly increased numbers of TdT-positive cells in acute lymphoblastic leukemia remission bone marrows (2%-7%) does not denote impending relapse. In addition, most of the patients with acute lymphoblastic leukemia in remission had less than 1% TdT-positive cells.

Previous studies have demonstrated that certain local juvenile periodontitis (LJP) patients possess neutrophils with an intrinsic chemotactic defect to the peptide chemoattractants f-met-leu-phe (FMLP) and C5a. In this investigation, the in vitro response of neutrophils to the chemotactic agent leukotriene B4 (LTB4) was examined. Those LJP patients who possessed defective chemotactic responses to FMLP and endotoxin activated serum (EAS) also had impaired chemotaxis to LTB4. Exogenous LTB4 failed to augment the impaired response to FMLP. Evidence for a global membrane defect in LJP neutrophils resulting in hyporesponsiveness to chemically diverse chemotactic agents is presented.