MRI of merkel cell carcinoma: histologic correlation and review of the literature

OBJECTIVE: The objective of this study was to determine the MRI characteristics of Merkel cell carcinoma, with an emphasis on histologic correlation. MATERIALS AND METHODS: The demographic information about 15 patients from our institution and their MRI examinations were retrospectively reviewed by three musculoskeletal radiologists by consensus for lesion location and intrinsic characteristics. The study group was composed of three women and 12 men who ranged in age from 48 to 87 years, with a mean age of 75 years. Histology results of resected specimens were reviewed in all cases and were correlated with imaging. RESULTS: MRI showed skin thickening, subcutaneous reticular stranding (n = 9, 60%); multiple anatomically aligned subcutaneous soft-tissue masses, representing lymphatic tumor nodules (n = 5, 33%); lymph node enlargement with fine, compressed, retained fatty tissue (n = 5, 33%); nodal necrosis (n = 1); and perifascial and intramuscular metastases (n = 2). Histology confirmed the lymphatic nature of the soft-tissue Merkel cell tumors. CONCLUSION: Patients with Merkel cell tumors may present at imaging with subcutaneous lymphatic reticular stranding, multiple subcutaneous masses, and lymph node metastases. Often there is massive lymph node enlargement with fine, compressed, retained fatty tissue.     

Dental aesthetics, self-awareness, and oral health-related quality of life in young adults

The aim of the present study was to explore the putative relationship between dental aesthetics and oral health-related quality of life (OHRQoL), taking into consideration the potential direct and moderating influence of private and public self-consciousness. The subjects of this cross-sectional survey were 148 university students. Dental aesthetics were assessed by means of the aesthetic component (AC) of the Index of Orthodontic Treatment Need (IOTN). OHRQoL was estimated using a modification of the scales 'social appearance concern' and 'appearance disapproval', and a novel dental self-confidence scale. In addition, the private and public self-consciousness scales were used. Two-factor analyses of variance were carried out with high and low levels of dental aesthetics and private and public self-consciousness as the independent variables and the OHRQoL scales as the dependent variables. It was found that dental aesthetics had a direct effect on all OHRQoL scale values. Private self-consciousness was related to social appearance concern, while public self-consciousness was associated with both social appearance concern and appearance disapproval. An interaction effect was identified which showed that the impact of dental aesthetics on social appearance concern was stronger in respondents with high private and public self-consciousness than in low scoring subjects. The findings of the study suggest that minor differences in dental aesthetics may have a significant effect on perceived OHRQoL. This effect was more significant in subjects with high self-consciousness.     

Wear of aluminum oxide antagonists by commercially available composites and compomers

PURPOSE: To investigate the wear of aluminum oxide antagonists by 19 light curing, commercially available composites and compomers. The influence of the filler particle size of the composites, the filler particle material and the filler particle morphology was determined. METHODS: Occlusal contact wear of the antagonists was simulated in a sliding wear test. Eight antagonists and specimens of each material were tested in a pin-on-block design with oscillating sliding of an aluminum oxide antagonist (Degussit antagonist, 5 mm diameter). After 50,000 cycles the contact area was evaluated using a dedicated software (UTHSCA image tool for windows V 2.0) under a light microscope. The size of the contact area was measured. RESULTS: Three types of boundaries of the contact area could be observed: (1) Sharp boundary, (2) No sharp boundary but easy to identify, and (3) No sharp boundary and difficult to identify. The method of Pearson was used to calculate the correlation coefficients. The coefficient of determination between the ranking of the measured contact area and the ranking of the maximum particle size was r2= 0.46 (P> 0.05). Composite materials with the same particle size were ranked by their filler content (wt. %).     

In vivo visualization of platelet/endothelium cell interaction in muscle flaps

Increasing evidence underlines the substantial pathophysiological impact of platelets on the development of ischemia/reperfusion injury (I/R) in flaps. Methods for studying dynamic platelet mechanisms in flaps in vivo are not available. The aim of this study was to develop a model enabling quantitative analysis of platelet kinetics and platelet-endothelium cell interaction within the microcirculation of muscle flaps in vivo. Balb/c mice (n = 16) were anesthetized, and an epigastric muscle flap was prepared. Autologous platelets were separated from blood donor animals (n = 16) and labeled ex vivo by means of rhodamine-6-G. After I/R (90 minutes' clamping, 10 minutes' reperfusion), the platelets were administered intra-arterially (i.a.). Microhemodynamics and kinetics of platelets were investigated by intravital fluorescence microscopy. I/R of muscle flaps induced disturbances in microcirculation. The number of rolling platelets, as well as platelets adhering to the inner vessel wall of venules, was increased in the ischemia group. Using intravital fluorescence microscopy, platelet kinetics were analyzed directly in flap microcirculation in vivo for the first time. Since platelet/endothelial cell interaction is a key event in the pathophysiology after microsurgical procedures, this model will help to understand basic molecular mechanisms of platelet behavior during I/R.     

Intraluminal laser light source and external solder: in vivo evaluation of a new technique for microvascular anastomosis

BACKGROUND AND OBJECTIVES: Current laser-assisted end-to-end anastomoses are performed by irradiating the vessel wall from outside after additional fixation with three to six sutures. These sutures are needed to provide adequate approximation of the vessel stumps. We present a new laser soldering technique that is based on an intraluminal laser light source centered in a balloon catheter, and external application of a solder. This technique was applied in vivo in order to test its feasibility under clinical conditions. STUDY DESIGN/MATERIALS AND METHODS: Seven white pigs were treated with a total of fourteen end-to-end laser-anastomoses of their saphenous arteries having outer diameters of 2 mm. The vessels were stented over an intraluminal balloon catheter, which was maximally dilated and which allowed for a precise approximation of the vascular stumps. An 808 nm diode laser was coupled into a specially designed optical fiber producing a 360 degrees radiation ring inside the balloon catheter. An indocyanine green (ICG) doped liquid albumin solder was applied on the external surface of the vascular stumps. Laser soldering was achieved by irradiating with a 808 nm laser diode for 75 seconds. Tightness of the anastomoses was evaluated by clamping the artery distal to the anastomosis for 1 hour, and patency was tested over an observation period of 3 hours, during which the animals were heparinized. Thereafter, the anastomoses were harvested for histomorphological examination. RESULTS: All anastomoses remained patent over the entire observation period. Some leakage was observed in three anastomoses, which was explained by a deviation of the illumination fiber from the center of the balloon leading to an inhomogeneous irradiation of the vessel wall. Histology revealed perfect adaptation of the vascular stumps. A segment of denaturated vascular collagen was observed, that corresponded to the irradiated, solder-covered zone. CONCLUSION: Patent, maximally dilated and well adapted microvascular anastomoses could be obtained without the need of stay sutures. A well centered laser light source is indispensable for avoiding inhomogenous welding, thus causing leakage.     

Impact of Site-Specific Nucleobase Deletions on the Arthritogenicity of DNA

Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG ODN) potently stimulate the innate and acquired immune system. We have compared the in vivo and in vitro inflammatogenic properties of CpG ODNs containing a specific nucleobase deletion either 5'-upstream (ODN-2) or 3'-downstream (ODN-3) of the CpG motif, comparing with a prototype CpG ODN (ODN-1). The frequency of arthritis was similar after intra-articular (i.a.) injections of ODN-1 or ODN-3, but was significantly lower (p < 0.02) after i.a. injections of ODN-2. In vitro production of the pro-inflammatory cytokine TNF-alpha was higher in mouse spleen cell cultures exposed to ODN-2 in comparison to ODN-1. In addition, the level of IL-10 induced by ODN-2 was higher than that induced by ODN-1. On the other hand, TNF-alpha, IL-10, and MCP-1 levels, as well as splenocyte proliferative responses were all significantly lower for ODN-3 than for ODN-1. These results suggest that a 5'-upstream nucleobase deletion reduces arthritogenicity, while maintaining or increasing the production of pro- and anti-inflammatory factors. In contrast, a 3'-downstream nucleobase deletion has no effect on arthritogenicity, despite significantly lower levels of proliferation and pro- and anti-inflammatory cytokines, compared with ODN-1. This study indicates that specific structural elements within the ODN sequence but outside the CpG motif, modulate the immunostimulatory properties of CpG ODNs.     

Lipopolysaccharide fever is initiated via a capsaicin-sensitive mechanism independent of the subtype-1 vanilloid receptor

As pretreatment with intraperitoneal capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP), an agonist of the vanilloid receptor known as VR1 or transient receptor potential channel-vanilloid receptor subtype 1 (TRPV-1), has been shown to block the first phase of lipopolysaccharide (LPS) fever in rats, this phase is thought to depend on the TRPV-1-bearing sensory nerve fibers originating in the abdominal cavity. However, our recent studies suggest that CAP blocks the first phase via a non-neural mechanism. In the present work, we studied whether this mechanism involves the TRPV-1. Adult Long-Evans rats implanted with chronic jugular catheters were used. Pretreatment with CAP (5 mg kg(-1), i.p.) 10 days before administration of LPS (10 microg kg(-1), i.v.) resulted in the loss of the entire first phase and a part of the second phase of LPS fever. Pretreatment with the ultrapotent TRPV-1 agonist resiniferatoxin (RTX; 2, 20, or 200 microg kg(-1), i.p.) 10 days before administration of LPS had no effect on the first and second phases of LPS fever, but it exaggerated the third phase at the highest dose. The latter effect was presumably due to the known ability of high doses of TRPV-1 agonists to cause a loss of warm sensitivity, thus leading to uncontrolled, hyperpyretic responses. Pretreatment with the selective competitive TRPV-1 antagonist capsazepine (N-[2-(4-chlorophenyl)ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2-benzazepine-2-carbothioamidem, CPZ; 40 mg kg(-1), i.p.) 90 min before administration of LPS (10 microg kg(-1), i.v.) or CAP (1 mg kg(-1), i.p.) did not affect LPS fever, but blocked the immediate hypothermic response to acute administration of CAP. It is concluded that LPS fever is initiated via a non-neural mechanism, which is CAP-sensitive but RTX- and CPZ-insensitive. The action of CAP on this mechanism is likely TRPV-1-independent. It is speculated that this mechanism may be the production of prostaglandin E(2) by macrophages in LPS-processing organs.     

Comprehensive strategy to prevent nosocomial spread of methicillin-resistant Staphylococcus aureus in a highly endemic setting

BACKGROUND: The effectiveness and feasibility of a comprehensive strategy to reduce nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) in a highly endemic setting have not yet been proved. Limited benefits and the high cost of such programs are the main concerns. METHODS: We prospectively evaluated the effect of an aggressive infection control program on transmission of MRSA in the University Clinic of Respiratory and Allergic Diseases. All patients with MRSA carriage during 5 years (January 1, 1998, through December 31, 2002) were included and categorized into imported or hospital-acquired cases. RESULTS: Methicillin-resistant S aureus was recovered from 223 hospitalized patients; 142 cases were imported and 81 were acquired at our institution. After introduction of the comprehensive infection control program in 1999, the annual incidence of MRSA carriage per 1000 admissions increased from 4.5 in 1998 to 8.0 in 1999 (P = .02), and remained stable thereafter. In this period, the proportion of MRSA cases acquired in our institution decreased from 50.0% in 1999 to 6.1% in 2002 (P<.001), whereas the proportion of MRSA cases transferred from other hospitals (P<.001) and nursing homes (P = .03) increased. All 19 MRSA carriers with 3 sets of follow-up cultures were successfully decolonized. CONCLUSIONS: With a comprehensive infection control program, it was possible to reduce nosocomial transmission of MRSA in a highly endemic setting. With good hand hygiene using alcohol handrub, early detection, isolation, and a decolonization strategy, containment of MRSA was achievable, despite a high rate of transferred patients with MRSA.     

P-selectin-targeting of the fibrin selective thrombolytic Desmodus rotundus salivary plasminogen activator alpha1

During thrombosis, P-selectin is expressed on the surface of activated endothelial cells and platelets. We hypothesized that targeting a plasminogen activator (PA) to P-selectin would enhance local thrombolysis and reduce bleeding risk. Previously, a urokinase (uPA)/anti-P-selectin antibody (HuSZ51) fusion protein was shown to increase fibrinolysis in a hamster pulmonary embolism model. To explore the therapeutic potential of this targeting strategy, we fused the fibrin-selective Desmodus rotundus salivary PA alpha1 (dsPA alpha 1) to HuSZ51 and compared the fibrinolytic activity of P-selectin-targeted dsPA alpha 1 (HuSZ51-dsPA alpha 1) to unmodified dsPA alpha 1 in vitro and in vivo. HuSZ51-dsPA alpha 1 and dsPA alpha 1 were expressed in CHO cells and purified to homogeneity by affinity chromatography. HuSZ51-dsPA alpha 1 bound to thrombin-activated human and dog platelets with comparable affinities to that of parental antibody SZ51. The fusion protein retained the catalytic activities of dsPA alpha 1 in chromogenic and clot lysis assays, indicating that dsPA alpha 1 is fully functional when fused to HuSZ51. Compared to dsPA alpha 1, HuSZ51-dsPA alpha 1 had similar thrombolytic efficacy in a rat pulmonary embolism model and anti-thrombotic potency in a dog model of femoral artery thrombosis. However, HuSZ51-dsPA alpha 1 was less effective in lysis of preexisting arterial thrombi in the dog model. The reduced arterial thrombolysis was not due to the pharmacokinetic properties of HuSZ51-dsPA alpha 1 because antigen level and amidolytic activity were higher in plasma from HuSZ51-dsPA alpha 1-treated groups than corresponding dsPA alpha 1-treated groups. These data indicate that the thrombolytic efficacy of HuSZ51-dsPA alpha 1 varied dependent on the physical composition of thrombi. The lack of stimulation by fibrin in arterial thrombi may contribute to the attenuated thrombolytic efficacy of HuSZ51-dsPA alpha 1 in the dog model.