Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families

REASONS FOR PERFORMING STUDY: The horse owner assessed respiratory signs index (HOARSI-1-4, healthy, mildly, moderately and severely affected, respectively) is based on owner-reported clinical history and has been used for the investigation of recurrent airway obstruction (RAO) genetics utilising large sample sizes. Reliable phenotype identification is of paramount importance in genetic studies. Owner reports of respiratory signs have shown good repeatability, but the agreement of HOARSI with an in-depth examination of the lower respiratory tract has not been investigated. OBJECTIVES: To determine the correlation of HOARSI grades 3/4 with the characteristics of RAO and of HOARSI-2 with the characteristics of inflammatory airway disease. Further, to test whether there are phenotypic differences in the manifestation of lung disease between families. METHODS: Seventy-one direct offspring of 2 RAO-affected Warmblood stallions (33 from the first family, 38 from the second) were graded as HOARSI-1-4 and underwent a clinical examination of the respiratory system, arterial blood gas analysis, endoscopic mucus scoring, cytology of tracheobronchial secretion (TBS) and bronchoalveolar lavage fluid (BALF), and clinical assessment of airway reactivity to methacholine chloride. RESULTS: HOARSI-3/4 animals in clinical exacerbation showed signs consistent with RAO: coughing, nasal discharge, abnormal lung sounds and breathing pattern as well as increased numbers of neutrophils in TBS and BALF, excessive mucus accumulation and airway hyper-responsiveness to methacholine. HOARSI-3/4 horses in remission only had increased amounts of tracheal mucus and TBS neutrophil percentages. Clinical phenotypes were not significantly different between the 2 families. CONCLUSIONS AND CLINICAL RELEVANCE: HOARSI reliably identifies RAO-affected horses in our population.

Tumor thrombus of inferior vena cava in patients with renal cell carcinoma - clinical and oncological outcome of 50 patients after surgery

Background To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC) and tumor thrombus involving inferior vena cava (IVC) treated with nephrectomy and thrombectomy. Methods We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome. Results The median follow-up was 26 months. In 21 patients (42%) distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30%), thoracoabdominal (14 patients/28%) or midline abdominal approach (21 patients/42%), depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB) was performed in 10 patients (20%) with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1%. Survival for the patients without distant metastasis at 5 years was 50.7%, whereas survival rate in the metastatic group at 5 years was 7.4%. Median survival of patients with metastatic disease was 16.4 months. On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10) even had a better outcome (overall survival at 5 years of 58.33%) than the entire cohort. Conclusions An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal circulation in patients with supradiaphragmal tumor thrombus. Cytoreductive surgery appears to be beneficial for patients with metastatic disease, especially when consecutive therapy is performed. Although sample size of our study cohort is limited consistent with some other studies lymph node invasion, distant metastasis and grading seem to have prognostic value.

Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease

BACKGROUND Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disease Initiative Study Group). One-hundred and eighty patients were evaluated using the Unified Huntington Disease Rating Scale over 36 months. A placebo effect was defined as an improvement of at least 50% over baseline scores in the Unified Huntington Disease Rating Scale, and clinically relevant when at least 10% of the population met it. RESULTS Only behavior showed a significant placebo effect, and the proportion of the patients with placebo effect ranged from 16% (first visit) to 41% (last visit). Nondepressed patients with better functional status were most likely to be placebo-responders over time. CONCLUSIONS In Huntington's disease, behavior seems to be more vulnerable to placebo than overall motor function, cognition, and function

Resonance frequency analysis in relation to jawbone characteristics and during early healing of implant installation

OBJECTIVES: To monitor resonance frequency analysis (RFA) in relation to the jawbone characteristics and during the early phases of healing and incorporation of Straumann dental implants with an SLA surface. MATERIAL AND METHODS: 17 Straumann 4.1 mm implants (10 mm) and 7 Straumann 4.8 mm implants (10 mm) were installed and ISQ determined at baseline and after 1, 2, 3, 4, 5, 6, 8 and 12 weeks. Central bone cores were analyzed from the 4.1 mm implants using micro CT for bone volume density (BVD) and bone trabecular connectivity (BTC). RESULTS: Pocket probing depths ranged from 2-4 mm and bleeding on probing from 5-20%. At baseline, BVD varied between 24% and 65% and BTC between 4.9 and 25.4 for the 4.1 mm implants. Baseline ISQ varied between 55 and 74 with a mean of 61.4. No significant correlations were found between BVD or BTC and ISQ Values. For the 4.8 mm diameter implants baseline ISQ values ranged from 57-70 with a mean of 63.3. Over the healing period ISQ values increased at 1 week and decreased after 2-3 weeks. After 4 weeks ISQ values, again increased slightly, no significant differences were noted over time. One implant (4.1 mm) lost stability at 3 weeks. Its ISQ value had dropped from 68 to 45. However the latter value was determined after the clinical diagnosis of instability. CONCLUSION: ISQ values of 57-70 represented homeostasis and implant stability. However no predictive value for loosing implant stability can be attributed to RFA since the decrease occurred after the fact.

Single-exposure dual-energy subtraction chest radiography: detection of pulmonary nodules and masses in clinical practice

The purpose of this retrospective study was to evaluate the impact of energy subtraction (ES) chest radiography on the detection of pulmonary nodules and masses in daily routine. Seventy-seven patients and 25 healthy subjects were examined with a single exposure digital radiography system. Five blinded readers evaluated first the non-subtracted PA and lateral chest radiographs alone and then together with the subtracted PA soft tissue images. The size, location and number of lung nodules or masses were registered with the confidence level. CT was used as standard of reference. For the 200 total lesions, a sensitivity of 33.5-52.5% was found at non-subtracted and a sensitivity of 43.5-58.5% at energy-subtracted radiography, corresponding to a significant improvement in four of five readers (p < 0.05). However, in three of five readers the rate of false positives was higher with ES. With ES, sensitivity, but not the area under the alternative free-response receiver operating characteristics (AFROC) curve, showed a good correlation with reader experience (R = 0.90, p = 0.026). In four of five readers, the diagnostic confidence improved with ES (p = 0.0036). We conclude that single-exposure digital ES chest radiography improves detection of most pulmonary nodules and masses, but identification of nodules <1 cm and false-positive findings remain a problem.

Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications

Although rare, stent thrombosis remains a severe complication after stent implantation owing to its high morbidity and mortality. Since the introduction of drug-eluting stents (DES), most interventional centers have noted stent thrombosis up to 3 years after implantation, a complication rarely seen with bare-metal stents. Some data from large registries and meta-analyses of randomized trials indicate a higher risk for DES thrombosis, whereas others suggest an absence of such a risk. Several factors are associated with an increased risk of stent thrombosis, including the procedure itself (stent malapposition and/or underexpansion, number of implanted stents, stent length, persistent slow coronary blood flow, and dissections), patient and lesion characteristics, stent design, and premature cessation of antiplatelet drugs. Drugs released from DES exert distinct biological effects, such as activation of signal transduction pathways and inhibition of cell proliferation. As a result, although primarily aimed at preventing vascular smooth muscle cell proliferation and migration (ie, key factors in the development of restenosis), they also impair reendothelialization, which leads to delayed arterial healing, and induce tissue factor expression, which results in a prothrombogenic environment. In the same way, polymers used to load these drugs have been associated with DES thrombosis. Finally, DES impair endothelial function of the coronary artery distal to the stent, which potentially promotes the risk of ischemia and coronary occlusion. Although several reports raise the possibility of a substantially higher risk of stent thrombosis in DES, evidence remains inconclusive; as a consequence, both large-scale and long-term clinical trials, as well as further mechanistic studies, are needed. The present review focuses on the pathophysiological mechanisms and pathological findings of stent thrombosis in DES.

Two-year clinical outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents in diabetic patients

Aims Percutaneous coronary intervention (PCI) in diabetic patients is associated with an increased risk of restenosis and major adverse cardiac events (MACE). We assessed the impact of diabetes on long-term outcome after PCI with sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents. Methods and results In the SIRTAX trial, 1012 patients were randomized to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of outcomes was performed according to the presence or absence of diabetes. Baseline characteristics were well balanced between SES and PES in patients with (N = 201) and without diabetes (N = 811). Clinical outcome was worse in diabetic compared with non-diabetic patients regarding death (9.0% vs. 4.1%, P = 0.004) and MACE (defined as cardiac death, myocardial infarction, or TLR; 19.9% vs. 12.7%, P = 0.007) at 2 years. Among diabetic patients, SES reduced MACE by 47% (14.8% vs. 25.8%, HR = 0.52, P = 0.05) and TLR by 61% (7.4% vs. 17.2%, HR = 0.39, P = 0.03) compared with PES at 2 years. Conclusion Diabetic patients have worse prognosis than non-diabetic patients undergoing PCI with DES. Among the diabetic patient population of this trial, SES reduce repeat revascularization procedures and MACE more effectively than PES and to a similar degree as in non-diabetic patients.

Monte Carlo source model for photon beam radiotherapy: photon source characteristics

A major barrier to widespread clinical implementation of Monte Carlo dose calculation is the difficulty in characterizing the radiation source within a generalized source model. This work aims to develop a generalized three-component source model (target, primary collimator, flattening filter) for 6- and 18-MV photon beams that match full phase-space data (PSD). Subsource by subsource comparison of dose distributions, using either source PSD or the source model as input, allows accurate source characterization and has the potential to ease the commissioning procedure, since it is possible to obtain information about which subsource needs to be tuned. This source model is unique in that, compared to previous source models, it retains additional correlations among PS variables, which improves accuracy at nonstandard source-to-surface distances (SSDs). In our study, three-dimensional (3D) dose calculations were performed for SSDs ranging from 50 to 200 cm and for field sizes from 1 x 1 to 30 x 30 cm2 as well as a 10 x 10 cm2 field 5 cm off axis in each direction. The 3D dose distributions, using either full PSD or the source model as input, were compared in terms of dose-difference and distance-to-agreement. With this model, over 99% of the voxels agreed within +/-1% or 1 mm for the target, within 2% or 2 mm for the primary collimator, and within +/-2.5% or 2 mm for the flattening filter in all cases studied. For the dose distributions, 99% of the dose voxels agreed within 1% or 1 mm when the combined source model-including a charged particle source and the full PSD as input-was used. The accurate and general characterization of each photon source and knowledge of the subsource dose distributions should facilitate source model commissioning procedures by allowing scaling the histogram distributions representing the subsources to be tuned.

Potential of chemically modified hydrophilic surface characteristics to support tissue integration of titanium dental implants

In the past, several modifications of specific surface properties such as topography, structure, chemistry, surface charge, and wettability have been investigated to predictably improve the osseointegration of titanium implants. The aim of the present review was to evaluate, based on the currently available evidence, the impact of hydrophilic surface modifications of titanium for dental implants. A surface treatment was performed to produce hydroxylated/hydrated titanium surfaces with identical microstructure to either acid-etched, or sand-blasted, large grit and acid-etched substrates, but with hydrophilic character. Preliminary in vitro studies have indicated that the specific properties noted for hydrophilic titanium surfaces have a significant influence on cell differentiation and growth factor production. Animal experiments have pointed out that hydrophilic surfaces improve early stages of soft tissue and hard tissue integration of either nonsubmerged or submerged titanium implants. This data was also corroborated by the results from preliminary clinical studies. In conclusion, the present review has pointed to a potential of hydrophilic surface modifications to support tissue integration of titanium dental implants.

Maxillary sinus grafting with Bio-Oss or Straumann Bone Ceramic: histomorphometric results from a randomized controlled multicenter clinical trial

INTRODUCTION: This investigation was designed to compare the histomorphometric results from sinus floor augmentation with anorganic bovine bone (ABB) and a new biphasic calcium phosphate, Straumann Bone Ceramic (BCP). MATERIALS AND METHODS: Forty-eight maxillary sinuses were treated in 37 patients. Residual bone width was > or =6 mm and height was > or =3 mm and <8 mm. Lateral sinus augmentation was used, with grafting using either ABB (control group; 23 sinuses) or BCP (test group; 25 sinuses); sites were randomly assigned to the control or test groups. After 180-240 days of healing, implant sites were created and biopsies taken for histological and histomorphometric analyses. The parameters assessed were (1) area fraction of new bone, soft tissue, and graft substitute material in the grafted region; (2) area fraction of bone and soft tissue components in the residual alveolar ridge compartment; and (3) the percentage of surface contact between the graft substitute material and new bone. RESULTS: Measurable biopsies were available from 56% of the test and 81.8% of the control sites. Histology showed close contact between new bone and graft particles for both groups, with no significant differences in the amount of mineralized bone (21.6+/-10.0% for BCP vs. 19.8+/-7.9% for ABB; P=0.53) in the biopsy treatment compartment of test and control site. The bone-to-graft contact was found to be significantly greater for ABB (48.2+/-12.9% vs. 34.0+/-14.0% for BCP). Significantly less remaining percentage of graft substitute material was found in the BCP group (26.6+/-5.2% vs. 37.7+/-8.5% for ABB; P=0.001), with more soft tissue components (46.4+/-7.7% vs. 40.4+/-7.3% for ABB; P=0.07). However, the amount of soft tissue components for both groups was found not to be greater than in the residual alveolar ridge. DISCUSSION: Both ABB and BCP produced similar amounts of newly formed bone, with similar histologic appearance, indicating that both materials are suitable for sinus augmentation for the placement of dental implants. The potential clinical relevance of more soft tissue components and different resorption characteristics of BCP requires further investigation.

Influence of suture tension to the tearing characteristics of the soft tissues: an in vitro experiment

OBJECTIVES: To evaluate the influence of flap tension on the tearing characteristics of mucosal tissue samples in relation to various suture and needle characteristics. MATERIAL AND METHODS: Lining and masticatory mucosal tissue samples obtained from pig jaws were prepared for in vitro testing. Tension tearing diagrams of 60 experiments were traced for 3-0, 5-0 and 7-0 sutures with applied forces up to 20 N. In the second part, the same experiments were repeated with 100 diagrams to test the influence of needle characteristics with 5-0 and 6-0 sutures using only gingival tissue samples. RESULTS: 3-0 sutures mainly lead to tissue breakage at an average of 13.4 N. In contrast, 7-0 sutures only resulted in breakage of the thread at a mean applied force of 3.7 N. With 5-0 sutures, both events occurred at random at a mean force of 14.6 N. Irrespective of the needle characteristics, the mean breaking force for gingival samples with 5-0 and 6-0 sutures was approximately 10 N. CONCLUSIONS: Tissue trauma may be reduced by choosing finer suture diameters, because thinner (6-0, 7-0) sutures lead to thread breakage rather than tissue breakage.

Basic and clinical immunology of Siglecs

Siglecs are cell-surface proteins found primarily on hematopoietic cells. By definition, they are members of the immunoglobulin gene super-family and bind sialic acid. Most contain cytoplasmic tyrosine motifs implicated in cell signaling. This review will first summarize characteristics common and unique to Siglecs, followed by a discussion of each human Siglec in numerical order, mentioning in turn its closest murine ortholog or paralog. Each section will describe its pattern of cellular expression, latest known immune functions, ligands, and signaling pathways, with the focus being predominantly on CD33-related Siglecs. Potential clinical and therapeutic implications of each Siglec will also be covered.

Clinical research projects at a German medical faculty: follow-up from ethical approval to publication and citation by others

BACKGROUND: Only data of published study results are available to the scientific community for further use such as informing future research and synthesis of available evidence. If study results are reported selectively, reporting bias and distortion of summarised estimates of effect or harm of treatments can occur. The publication and citation of results of clinical research conducted in Germany was studied. METHODS: The protocols of clinical research projects submitted to the research ethics committee of the University of Freiburg (Germany) in 2000 were analysed. Published full articles in several databases were searched and investigators contacted. Data on study and publication characteristics were extracted from protocols and corresponding publications. RESULTS: 299 study protocols were included. The most frequent study design was randomised controlled trial (141; 47%), followed by uncontrolled studies (61; 20%), laboratory studies (30; 10%) and non-randomised studies (29; 10%). 182 (61%) were multicentre studies including 97 (53%) international collaborations. 152 of 299 (51%) had commercial (co-)funding and 46 (15%) non-commercial funding. 109 of the 225 completed protocols corresponded to at least one full publication (total 210 articles); the publication rate was 48%. 168 of 210 identified publications (80%) were cited in articles indexed in the ISI Web of Science. The median was 11 citations per publication (range 0-1151). CONCLUSIONS: Results of German clinical research projects conducted are largely underreported. Barriers to successful publication need to be identified and appropriate measures taken. Close monitoring of projects until publication and adequate support provided to investigators may help remedy the prevailing underreporting of research.

Recurrence characteristics in European patients with ocular toxoplasmosis

BACKGROUND: The risk of function loss after each episode of ocular toxoplasmosis (OT) supports efforts to improve our understanding of the disease. Patients and methods: 139 patients with OT were contacted retrospectively and requested to complete a questionnaire addressing course and activity of their disease. This information was compared with that retrieved from their medical records. Sixty-three patients completed the questionnaire and were included in the study. They were allocated according to their median age to one of two groups (group 1: <20.9 years; group 2: >or=20.9 years). RESULTS: The mean reported age at the time of first ocular manifestation was 23.9 (median 20.9, range 0 to 70.5; SD 12.9) years. The clinical diagnosis was made 3.5 years later (p = 0.0008). The follow-up time was 6.5 (median 5.0; range 0.5 to 49.9; SD 7.6) years. The recurrence rate was higher in patients below 20.9 years (66%; n = 35) than in older patients (39%; n = 28; chi(2) test, p<0.05). Patients reporting only one episode were older at first manifestation (29.6 (median 25.6; range 10.6 to 70.5; SD 14.3) years; n = 29) than those reporting two episodes (17.9 (median 19.5; range 5.9 to 33.9; SD 7.8) years; n = 15 (p<0.05)). The proportion of patients who developed a recurrence was 54-63% after each episode without a tendency to enlarge, and the interval between successive episodes remained stable between 1.0 and 1.7 years for the first three recurrences. CONCLUSION: Younger OT patients carry a higher risk of developing a recurrence than older ones. After each episode, two-thirds of all OT patients will develop another one.

Does aortic crossclamping during the cooling phase affect the early clinical outcome of acute type A aortic dissection?

OBJECTIVES: The purpose of this study is to evaluate the effects of crossclamping the ascending aorta in acute type A aortic dissection during the cooling phase for deep hypothermic arrest on early clinical outcome. METHODS: The records of 275 consecutive patients who underwent surgery for acute type A aortic dissection were reviewed. Ten patients have been excluded. Overall, 265 patients who underwent surgery under deep hypothermia and circulatory arrest in the "open technique" were divided retrospectively into two groups: those who underwent surgery with crossclamping of the ascending aorta during the cooling phase at the begin of the procedure (group 1, n = 191; 72.1 %) and those in whom the aorta was not clamped (group 2, n = 74; 27.9 %). RESULTS: Preoperative characteristics were similar in both groups. In group 1, femoral artery cannulation, composite graft repair, and aortic arch replacement were significantly more frequent. In-hospital mortality was 15.2 % in group 1 and 17.6 % in group 2 (P = not significant). Neurologic deficits were observed in 9.4% in group 1 and in 10.8% in group 2 (= not significant). There were no significant differences in clinical outcome between the two groups of patients. CONCLUSIONS: This study demonstrates that both options, aortic crossclamping or noclamping, may be used during the induction of deep hypothermia to repair acute type A aortic dissections with similar early clinical outcome. For the selection of the most appropriate technique, we recommend case by case evaluation, weighing the potential risks and benefits of aortic crossclamping.