Clinical and radiographic evaluation of intrabony periodontal defect treatment by open flap debridement alone or in combination with nanocrystalline hydroxyapatite bone substitute

The aim of this study has been to compare the clinical and radiographic outcome of periodontal intrabony defect treatment by open flap debridement alone or in combination with nanocrystalline hydroxyapatite bone substitute application. Thirty patients diagnosed with advanced periodontits were divided into two groups: the control group (OFD), in which an open flap debridement procedure was performed and the test group (OFD+NHA), in which defects were additionally filled with nanocrystalline hydroxyapatite bone substitute material. Plaque index (PI), gingival index (GI), bleeding on probing (BOP), pocket depth (PD), gingival recession (GR) and clinical attachment level (CAL) were measured prior to, then 6 and 12months following treatment. Radiographic depth and width of defects were also evaluated. There were no differences in any clinical and radiographic parameters between the examined groups prior to treatment. After treatment, BOP, GI, PD, CAL, radiographic depth and width parameter values improved statistically significantly in both groups. The PI value did not change, but the GR value increased significantly after treatment. There were no statistical differences in evaluated parameters between OFD and OFD+NHA groups 6 and 12months after treatment. Within the limits of the study, it can be concluded that the additional use of nanocrystalline hydroxyapatite bone substitute material after open flap procedure does not improve clinical and radiographic treatment outcome.

Osteoblast proliferation and differentiation on a barrier membrane in combination with BMP2 and TGFβ1

Bioresorbable collagen membranes are routinely utilized in guided bone regeneration to selectively direct the growth and repopulation of bone cells in areas of insufficient volume. However, the exact nature by which alveolar osteoblasts react to barrier membranes as well as the effects following the addition of growth factors to the membranes are still poorly understood. The objective of the present study was therefore to investigate the effect of a bioresorbable collagen membrane soak-loaded in growth factors bone morphogenetic protein 2 (BMP2) or transforming growth factor β1 (TGFβ1) on osteoblast adhesion, proliferation, and differentiation.

Patterns of molecular response to and relapse after combination of sorafenib, idarubicin, and cytarabine in patients with FLT3 mutant acute myeloid leukemia

BACKGROUND: FMS-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase involved in hematopoietic progenitor cell development. Mutations of FLT3 have been reported in about a third of patients with acute myeloid leukemia (AML), and inhibitors of FLT3 are of clinical interest. Sorafenib is an orally active multikinase inhibitor with potent activity against FLT3 and the Raf/ERK/MEK kinase pathway. METHODS: We studied the patterns of molecular response and relapse in 18 patients with mutated FLT3 treated with the combination of sorafenib, idarubicin, and cytarabine. RESULTS: The median follow-up was 9 months. Sixteen patients achieved complete remission (CR), and the other 2 patients achieved CR but lacked platelet recovery for an overall response rate of 100%. Ten patients had their FLT3-mutated clone eradicated, with 6 patients who showed some residual FLT3-mutated cells, and 2 patients who showed persistent FLT3-mutated cells. The elimination of FLT3-mutated population at the time of morphologic CR, however, was not predictive of relapse. After a median follow-up of 9 months (range, 1-16 months), 10 (55%) patients had relapsed, with a median CR duration of 8.8 months (range, 1-9.5 months). By DNA sequencing, there was no evidence of an acquired FLT3 point mutation at the time of relapse in 7 patients tested, which suggested the presence of other mechanisms of sorafenib resistance. CONCLUSION: Sorafenib, combined with chemotherapy, is effective in attaining CR, but relapses still occur.

Best combination of pre-stimulation and latency period duration before cluster attachment for efficient oxytocin release and milk ejection in cows with low to high udder-filling levels

Experiments were designed to investigate the suitability of a combination of a short manual teat stimulation with a short latency period before teat cup attachment to induce and maintain oxytocin release and milk ejection without interruption. In Experiment 1, seven dairy cows in mid lactation were manually pre-stimulated for 15, 30 or 45 s, followed by either 30 s or 45 s of latency period. It was shown that all treatments induced a similar release of oxytocin without interruption until the end of milking. In particular, the latency period of up to 45 s did not cause a transient decrease of oxytocin concentration. In Experiment 2, milking characteristics were recorded in seven cows each in early, mid, and late lactation, respectively. Because the course of milk ejection depends mainly on the degree of udder filling, individual milkings were classified based on the actual degree of udder filling which differs between lactational stages but also between morning and evening milkings. All animals underwent twelve different udder preparation treatments, i.e. 15, 30, or 45 s of pre-stimulation followed by latency periods of 0, 30, 45, or 60 s. Milking characteristics were recorded. Total milk yield, main milking time and average milk flow rate did not differ between treatments if the degree of udder filling at the start of milking was >40% of the maximum storage capacity. However, if the udder filling was <40%, main milking time was decreased with the duration of a latency period up to 45 s, independent of duration of pre-stimulation. Average milk flow at an udder filling of <40% was highest after a pre-stimulation of 45 s followed by a latency period of another 45 s. In contrast, average milk flow reached its lowest values at a pre-stimulation of 15 s without additional latency period. However, average milk flow after a 15-s pre-stimulation increased with increasing latency period. In conclusion, a very short pre-stimulation when followed by a latency period up to 45 s before teat cup attachment remains a suitable alternative for continuous stimulation to induce milk ejection.

Pathology hinting as the combination of automatic segmentation with a statistical shape model

With improvements in acquisition speed and quality, the amount of medical image data to be screened by clinicians is starting to become challenging in the daily clinical practice. To quickly visualize and find abnormalities in medical images, we propose a new method combining segmentation algorithms with statistical shape models. A statistical shape model built from a healthy population will have a close fit in healthy regions. The model will however not fit to morphological abnormalities often present in the areas of pathologies. Using the residual fitting error of the statistical shape model, pathologies can be visualized very quickly. This idea is applied to finding drusen in the retinal pigment epithelium (RPE) of optical coherence tomography (OCT) volumes. A segmentation technique able to accurately segment drusen in patients with age-related macular degeneration (AMD) is applied. The segmentation is then analyzed with a statistical shape model to visualize potentially pathological areas. An extensive evaluation is performed to validate the segmentation algorithm, as well as the quality and sensitivity of the hinting system. Most of the drusen with a height of 85.5 microm were detected, and all drusen at least 93.6 microm high were detected.

Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy

To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy.

Phase I trial of combretastatin A4 phosphate (CA4P) in combination with bevacizumab in patients with advanced cancer

The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to a VDA attenuates the revascularization of the surviving tumor rim and thus significantly increases antitumor activity.

Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers

Substantial variation exists in response to standard doses of codeine ranging from poor analgesia to life-threatening central nervous system (CNS) depression. We aimed to discover the genetic markers predictive of codeine toxicity by evaluating the associations between polymorphisms in cytochrome P450 2D6 (CYP2D6), UDP-glucuronosyltransferase 2B7 (UGT2B7), P-glycoprotein (ABCB1), mu-opioid receptor (OPRM1), and catechol O-methyltransferase (COMT) genes, which are involved in the codeine pathway, and the symptoms of CNS depression in 111 breastfeeding mothers using codeine and their infants. A genetic model combining the maternal risk genotypes in CYP2D6 and ABCB1 was significantly associated with the adverse outcomes in infants (odds ratio (OR) 2.68; 95% confidence interval (CI) 1.61-4.48; P(trend) = 0.0002) and their mothers (OR 2.74; 95% CI 1.55-4.84; P(trend) = 0.0005). A novel combination of the genetic and clinical factors predicted 87% of the infant and maternal CNS depression cases with a sensitivity of 80% and a specificity of 87%. Genetic markers can be used to improve the outcome of codeine therapy and are also probably important for other opioids sharing common biotransformation pathways.

Choice of Initial Combination Antiretroviral Therapy in Individuals With HIV Infection: Determinants and Outcomes

BACKGROUND Current guidelines give recommendations for preferred combination antiretroviral therapy (cART). We investigated factors influencing the choice of initial cART in clinical practice and its outcome. METHODS We analyzed treatment-naive adults with human immunodeficiency virus (HIV) infection participating in the Swiss HIV Cohort Study and starting cART from January 1, 2005, through December 31, 2009. The primary end point was the choice of the initial antiretroviral regimen. Secondary end points were virologic suppression, the increase in CD4 cell counts from baseline, and treatment modification within 12 months after starting treatment. RESULTS A total of 1957 patients were analyzed. Tenofovir-emtricitabine (TDF-FTC)-efavirenz was the most frequently prescribed cART (29.9%), followed by TDF-FTC-lopinavir/r (16.9%), TDF-FTC-atazanavir/r (12.9%), zidovudine-lamivudine (ZDV-3TC)-lopinavir/r (12.8%), and abacavir/lamivudine (ABC-3TC)-efavirenz (5.7%). Differences in prescription were noted among different Swiss HIV Cohort Study sites (P < .001). In multivariate analysis, compared with TDF-FTC-efavirenz, starting TDF-FTC-lopinavir/r was associated with prior AIDS (relative risk ratio, 2.78; 95% CI, 1.78-4.35), HIV-RNA greater than 100 000 copies/mL (1.53; 1.07-2.18), and CD4 greater than 350 cells/μL (1.67; 1.04-2.70); TDF-FTC-atazanavir/r with a depressive disorder (1.77; 1.04-3.01), HIV-RNA greater than 100 000 copies/mL (1.54; 1.05-2.25), and an opiate substitution program (2.76; 1.09-7.00); and ZDV-3TC-lopinavir/r with female sex (3.89; 2.39-6.31) and CD4 cell counts greater than 350 cells/μL (4.50; 2.58-7.86). At 12 months, 1715 patients (87.6%) achieved viral load less than 50 copies/mL and CD4 cell counts increased by a median (interquartile range) of 173 (89-269) cells/μL. Virologic suppression was more likely with TDF-FTC-efavirenz, and CD4 increase was higher with ZDV-3TC-lopinavir/r. No differences in outcome were observed among Swiss HIV Cohort Study sites. CONCLUSIONS Large differences in prescription but not in outcome were observed among study sites. A trend toward individualized cART was noted suggesting that initial cART is significantly influenced by physician's preference and patient characteristics. Our study highlights the need for evidence-based data for determining the best initial regimen for different HIV-infected persons.

Longer prior exposure to zidovudine/lamivudine-containing combination antiretroviral therapy, age, and male gender are each associated with reduced subcutaneous adipose tissue

Whether zidovudine (AZT)-associated lipoatrophy occurrence differs by concomitant exposure to protease (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains unclear. Baseline body composition data from a randomized trial in subjects stable on first-line AZT-based therapy were used to explore this issue.

CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE

Background Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. Methods and Findings Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements <50 copies/µl and ending with either a measurement >500 copies/µl, the first of two consecutive measurements between 50–500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30–0.40) for counts <200 cells/µl, 0.81 (0.71–0.92) for counts 200 to <350 cells/µl, 0.74 (0.66–0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92–0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. Conclusions Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

[Arterial Hypertension - when are which combination therapies useful?]

Arterial hypertension is a widely prevalent risk factor for cardiovascular diseases with well documented harmful effects on the heart and the vascular system. Despite a broad antihypertensive drug armamentarium control of hypertension is worldwide suboptimal. Daily practice as well as large intervention trials show that single-drug therapy often fails to adequately control blood pressure (BP). Therefore, the early introduction of a combination therapy may lead to a better and more rapid BP lowering effect, particularly in patients with more than stage I hypertension or in patients with mild hypertension and high cardiovascular risk. In addition, side effects of an antihypertensive drug can be prevented by a meaningful (low dose) combination with a second antihypertensive agent. Moreover, combination of antihypertensive drugs, especially if provided fixed, may substantially improve compliance. However, the choice of the drug combination primarily relates on the demographic features and co-morbidities of the patient. Although BP lowering is the main determinant of cardiovascular risk reduction in the treatment of hypertension, some antihypertensive drugs may exhibit protective effects beyond BP reduction that have to be considered when antihypertensive drugs are combined. In recent large intervention studies, the combination of an ACE inhibitor with a calcium channel blocker was especially advantageous in high risk hypertensive patients. The addition of a thiazide type diuretic to a blocker of the renin-angiotensin system is also sensible and popular with numerous available fixed combinations.