Local interaction of apoptotic hepatocytes and Kupffer cells in a rat model of systemic endotoxemia

Aim: There is strong evidence that hepatocellular apoptosis is not only initiated by circulating blood cells which become adherent within the endotoxemic liver, but also contributes to further sustain the inflammatory cell-cell response. Methods: Because previous studies assumed the importance of the role of cellular cross-talk in mediating inflammatory liver injury, we herein examined the activation of Kupffer cells (KCs) and their spatial coincidence with intrahepatic leukocyte adherence and hepatocellular apoptosis at 6 h after intraperitoneal exposure of rats with lipopolysaccharide (10 mg/kg). Results: In vivo multifluorescence microscopy revealed liver injury including nutritive perfusion failure, tissue hypoxia, leukocyte accumulation, as well as KC activation and parenchymal apoptotic cell death. Detailed spatial analysis revealed frequent colocalization of activated KCs with apoptotic hepatocytes. Colocalization was absent in saline-treated controls.Colocalization was confirmed by histochemistry, which showed ED1-positive KCs neighboring and engulfing TUNEL-positive hepatocytes. Colocalization of KCs with leukocytes ranged between 4% and 5% and did not increase in endotoxemic animals. Taken together, the present results indicate that apoptotic cell death of hepatocytes may stimulate phagocytosis by neighboring KCs. Direct KC-leukocyte contact seems not to be mandatory for cellular communication in the process of hepatocellular apoptosis. Conclusion: With respect to the fundamental importance of cell apoptosis, improved knowledge of these cell-cell interactions might allow the development of new therapeutic strategies through the regulation of apoptotic cell death.     

Near fatal infection of a patient with a left ventricular assist device due to unrecognized fetal death.

We report on an unusual case of a young female patient who received an implantable LVAD after unsuccessful emergency coronary bypass surgery following acute myocardial infarction. After LVAD placement, it became evident that the patient had been pregnant. She had to undergo gynaecological surgery during mechanical support to remove the deceased fetus.     

Verifikation und Anwendungen des voxelbasierten Monte-Carlo-(VMC++-)Elektronen-Dosismoduls von Oncentra™ MasterPlan

PURPOSE, MATERIAL AND METHODS: The dose calculation accuracy of the voxel-based Monte Carlo (VMC++) electron dose module of Oncentra MasterPlan (Nucletron B.V., Veenendaal, The Netherlands) was verified by measurements in homogeneous water phantoms. RESULTS: Measured and calculated dose maxima on the central beam axis (calculations with 10,000-20,000 incident electron histories per cm(2)) agree well using standard applicator configurations as well as individually shaped inserts. Profile scans with higher electron energies (>/= 15 MeV) reveal differences up to 5% especially in the penumbra region. Depth dose curves agree best in the vicinity of maximum depths. In the buildup region energy-dependent differences up to 5% in both directions could be observed. In the decay region of depth dose curves calculated doses were up to 10% higher than measured values. CONCLUSION: Good VMC++ accuracy combined with moderate computing times of 1-15 min per beam satisfy all clinical needs. VMC++ allows, for the first time, accurate routine dose evaluations of radiation therapy with electrons. Adequate positioning of the dose reference point is essential. Even small displacements may significantly influence the calculation of monitor units.     

The use of telescoping guide catheters for coronary sinus cannulation and sub-selecting tributaries in left ventricular lead placement

Introduction Failure to enter the coronary sinus (CS) with a guiding catheter and entering its tributaries remains challenging in left ventricle (LV) pacing lead implants for cardiac resynchronization therapy (CRT). A dual telescoping catheter system (8F outer/6F inner) is designed to provide the ability to adjust the catheter curve size, shape and/or reach to the patients’ anatomy avoiding the need for catheter change. Methods Five different designs for CS cannulation were randomly tested in 64 patients scheduled for CRT device implant. Results In 33 consecutive patients three adaptable telescoping guiding catheter systems were tested per patient, the adaptable catheters had higher overall cannulation success rates (68, 63 and 62%) compared to the fixed shape catheter (46%) and an greater cannulation success rate when the CS location was not known (70, 53 and 72% vs 33% for the fixed shape). In a second group of 31 CRT patients the two telescoping catheters had similar high levels of success (71–80%), with or without using the inner catheter. Conclusions The telescopic system is adaptable to a wide range of anatomical variations in patients and can result in a higher CS cannulation success rate due to its adjustability in the RA in search for the CS ostium. On top of this the inner catheter allows for sub-selecting the CS tributaries.     

Degradable injectable bone cement in maxillofacial surgery: indications and clinical experience in 27 patients.

BACKGROUND: A carbonated apatite cement (NORIAN SRS) was used as a bone mineral substitute for the calvaria or viscerocranium in 27 patients. It has the consistency of a paste and hardens at physiologic pH and body temperature due to dahllite crystallization, which has the stoichiometric formula Ca(8.8)(HPO(4))(0.7)(PO(4))(4.5)(CO(3))(0.7)(OH)(1.3). MATERIAL AND METHODS: The cement was used for posttraumatic bone defects in the orbital, periorbital or malar regions (nine patients), posttraumatic deformities of the frontal bone (six patients), tumour-dependent bony defects of the calvaria (two patients) and posttraumatic or cystic defects of the mandible (five patients). In another five patients, the material was used to augment the atrophic anterior mandible in combination with the insertion of dental implants. Follow-up varied between 6 and 40 months (mean: 29 months). RESULTS: There was no inflammatory reaction surrounding the implanted material. There was no sign of infection in any of the patients and only one case of partial wound dehiscence with superficially exposed material. The defect fillings and augmentations were successful in all patients. None of the 19 dental implants which were inserted in combination with the material showed any sign of infection or loosening. Also, there was no loosening of the implants after loading (mean follow-up: 15 months). From the check-up radiographs, the material could be seen as a dense, radio-opaque structure. There were no material fractures or dislocations. Radiologically, the material seemed to be completely replaced by bony tissue after 30 months. CONCLUSION: Our 5-year clinical experience suggests that the material is a suitable bone mineral substitute for cranio-maxillofacial surgery especially for moderate-sized defects of the calvaria and forehead bone. It has advantages over preformed, solid bone substitute materials, and, due to its initial plasticity and eventual great compressive strength, it can also stabilize dental endosseous implants in the atrophic mandible.     

Prognostic factors in surgically resected N2 non-small cell lung cancer: the importance of patterns of mediastinal lymph nodes metastases.

OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) with metastases to ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients as regard to prognosis and treatment. Indication and timing of surgery remain controversial. The present study investigates the prognostic factors, in order to identify homogenous subgroups of patients. METHODS: Histologically proven N2-NSCLC patients, who underwent a complete surgical resection were retrospectively reviewed. Clinical and pathological features were reported and analyzed, and survival study was performed. RESULTS: One hundred eighty-three patients were analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and 20%, with a median survival time of 24 months. Univariate analysis showed a significant better prognosis for: incidental N2 respect to clinical N2 (5-years 35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5-years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe tumors with superior mediastinal nodes and left upper lobe tumors with aortic nodes respect to lower lobes tumors with lower mediastinal nodes (5-years 31.8 and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage respect to continuous lymphatic spread. N2 clinical status, the number of levels involved and the two specific patterns of lymphatic spread resulted significant prognostic factors at multivariate analysis. CONCLUSIONS: Clinical N2 status, number of lymph nodes levels involved and specific patterns of lymphatic spread identify homogenous subgroups of patients that can be proposed for different therapeutic strategies.     

BoneMorphing versus freehand localization of anatomical landmarks: consequences for the reproducibility of implant positioning in total knee arthroplasty.

OBJECTIVE: This study analyzed the influence of the acquisition method in image-free computer-assisted total knee arthroplasty (CAS-TKA), and the reproducibility of implant planning using BoneMorphing, a 3D morphometric model obtained by a 3D-to-3D elastic registration of statistical models to sparse point clouds acquired directly on the bone surface with a pointer. MATERIALS AND METHODS: Five surgeons (one expert, four trainees) each performed a CAS-TKA hybrid protocol based on morphometric models and landmarks on a cadaveric knee 10 times. In addition, several additional landmarks were digitized during each acquisition. The reproducibility of the implant positioning and sizing, as determined by an implant planning algorithm with morphometric models, was compared to direct digitization accuracy. RESULTS: Femoral and tibial implant positioning parameters with the hybrid protocol resulted in intra-surgeon standard deviations (SDs) of less than+/-1.4 degrees for rotation and 1.9 mm for translation for all surgeons in all directions except for tibial axial rotation (the only parameter determined by a digitized landmark and not recomputed in the 3D model). The variability in individual landmark digitization varied from 2 to 5 mm SD for certain landmarks, with ranges of 15-25 mm across all surgeons. The comparison study showed an improvement in femoral rotation reproducibility with the morphometric model when using the posterior condylar axis. Tibial implant reproducibility for each method was comparable, with the morphometric model giving better results in well-digitized areas such as the tibial plateau. CONCLUSION: A CAS-TKA protocol based on a deformed statistical model offers reproducible implant positioning. Some landmarks, such as distal condyles, show sufficient reproducibility in the direction of interest, while others, such as the anterior tibial tubercle, can lead to hazardous implant positioning. This should be taken into consideration when designing a CAS-TKA system with bony landmarks. In areas where a sufficient number of points have been digitized with good coverage, such as on the distal and posterior femoral condyles or the tibial plateau areas, the information derived from the 3D model is more accurate and reproducible than that derived from digitization. Good training and a guiding user interface are essential to guarantee coverage quality.     

Whole-Blood Assay to Measure Oxidative Burst and Degranulation of Neutrophils for Monitoring Trauma Patients

AbstractBackground and Purpose: Polymorphonuclear neutrophils (PMNs) protect the host from invading microorganisms, but excessive PMN activation after trauma causes tissue injury. Rapid monitoring of PMN function is critical for the assessment of the inflammatory state of trauma patients. Here, the authors adapted two simple and rapid methods to measure oxidative burst and degranulation of human PMNs in whole blood to avoid potential interference of cell isolation procedures with the assessment of PMN function.Material and Methods: Heparinized blood was drawn from healthy volunteers or trauma patients, preincubated at 37 °C for 5 min, and stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP). Four assays for oxidative burst were tested: (1) cytochrome C; (2) homovanillic acid (HVA); (3) Amplex^® Red; and (4) flow cytometry with dihydrorhodamine 123 (DHR). PMN degranulation was assessed with flow cytometry using antibodies to: (1) CD11b/Mac-1 (CD18); (2) CD63; and (3) CD66b (CD67).Results: With the exception of the DHR method, all methods to measure oxidative burst were found to be unsuitable in whole blood due to interference of plasma proteins and hemoglobin with the fluorimetric or photometric readouts. By contrast, all degranulation methods were suitable for whole-blood studies. However, for the assessment of formyl peptide-induced degranulation, anti-antibodies to CD11b/Mac-1 and CD66b were up to five times more sensitive than antibodies to CD63. Thus, the degranulation and DHR methods were optimized for increased sensitivity, speed, and specificity and their usefulness to measure PMN function in trauma patients was tested.Conclusion: The whole-blood methods based on flow cytometry with DHR, anti-CD11b/Mac-1, and anti- CD66b are rapid, simple, and reliable techniques to assess PMN function for trauma research.     

Effect of Mutans streptococcal colonization on plaque formation and regrowth in young children--a brief commnunication.

OBJECTIVES: Visible plaque on the maxillary anterior teeth of young children has been identified as a risk indicator for early childhood caries. The present study examined whether this plaque is related to the colonization of children's teeth with Mutans streptococci (MS) or toothbrushing frequency. METHODS: Thirty-nine children, aged 12 to 36 months, had plaque scores, and plaque samples were taken from the labial surfaces of the maxillary incisors at baseline and repeated 3 days after suspended oral hygiene (plaque regrowth). RESULTS: A positive correlation was found between the baseline percent MS and regrowth plaque score and between baseline and regrowth plaque scores. Plaque scores of those that brushed zero to one time a day were not different from those who brushed two or more times a day. CONCLUSIONS: This study suggests that the presence of plaque on the anterior teeth of young children is consistent and related to MS colonization.