Frameless image guidance improves accuracy in three-dimensional interstitial brachytherapy needle placement

PURPOSE: The aim of this work was to adapt a computer-assisted real-time three-dimensional (3D) navigation system for interstitial brachytherapy procedures. METHODS AND MATERIALS: The 3-D navigation system Surgical Planning and Orientation Computer System (SPOCS; Aesculap, Tuttlingen, Germany) was adapted for use in interstitial brachytherapy. A special needle holder with mounted infrared-emitting diodes (IRED) for 3D navigation-based needle implantation was developed. Measurements were made on a series of different phantoms to study the feasibility and the overall accuracy and precision of the navigation system with regard to single-needle application and volume implants (multiple-needle implantations). In all, 250 single implants and 20 volume implants were performed. Accuracy was measured as the target registration error (TRE) between the preoperatively defined and the achieved target position. RESULTS: Analyses of the 250 different targets showed a mean TRE for single-needle applications of 1.1 mm (SD +/- 0.4 mm), 0.9 mm (SD +/- 0.3 mm), and 0.7 mm (SD +/- 0.3 mm) in the x, y, and z direction, respectively. The maximal deviation was 2.3 mm. The corresponding TRE in the x, y, and z direction for volume implants was 1.6 mm (SD +/- 0.4 mm), 1.9 mm (SD +/- 0.6 mm), and 1.0 mm (SD +/- 0.4 mm), respectively. The maximum deviation was 2.9 mm. CONCLUSIONS: The adaptation of a commercially available surgical planning and navigation system to interstitial brachytherapy is feasible. It enables virtual planning and improved accuracy in 3D interstitial needle implantation.     

Mitochondrial p53 levels parallel total p53 levels independent of stress response in human colorectal carcinoma and glioblastoma cells

p53 can eliminate damaged cells through the induction of mitochondria-mediated apoptosis. Recent observations have provided strong evidence that a fraction of total p53 translocates to mitochondria specifically in response to a death stimulus. Unexpectedly, mutant p53, which is expressed at much higher levels than wild type in unstressed cells, is apparently always present at the mitochondria, independent of apoptotic signal. This prompted us to ask whether cell lines with intact p53-dependent apoptosis and cell cycle arrest pathways exist in which the mitochondrial localization of wild-type p53, like that of mutant, is independent of a death stimulus and instead, correlates with the total p53 levels. Here, we document that human HCT116 colorectal carcinoma cells treated with adriamycin or 5-fluorouracil (5FU) can accumulate total p53 to equally high levels, and mitochondrial p53 to proportionate levels, although only 5FU treatment provoked p53-dependent apoptosis. Along the same line, HCT116 derivatives with increased basal p53 levels, and glioblastoma cells with a doxycycline-inducible p53, also revealed proportionate mitochondrial p53 levels, and even unstressed HCT116 cells had some p53 located at the mitochondria. Finally, mitochondrial and total p53 showed distinct post-translational modifications. Thus, cell lines exist in which the mitochondrial p53 levels parallel total levels independent of apoptosis.     

Gender-specific risk of perioperative complications in carotid endarterectomy patients with contralateral carotid artery stenosis or occlusion

Carotid endarterectomy (CEA) has been shown to be effective in stroke prevention in selected patients. Some studies, however, identified gender as an independent risk factor for perioperative CEA complications demonstrating an increased rate of perioperative stroke or death in women. Furthermore, contralateral internal carotid artery (ICA) occlusion has been associated with higher rates of perioperative CEA complications. Therefore, we sought to analyse the gender-specific risk of perioperative CEA complications between patients with or without contralateral ICA stenosis or occlusion. We retrospectively analysed 212 consecutive CEA patients (male = 156, Female = 56) for their gender-specific, perioperative risk of stroke, transient ischemic attack (TIA), restenosis and cardiac complications in the presence (62%) or absence (38%) of a contralateral ICA stenosis/occlusion. In women but not in men, risk of perioperative ischemic events (stroke, TIA) or re-stenosis (p = 0.036) and combined perioperative complications (ischemic events, re-stenosis or cardiac complications; 38.2 % vs. 9.1%; p = 0.028) was significantly increased in the presence of a contralateral ICA stenosis or occlusion. Furthermore, in the presence of a contralateral ICA stenosis/occlusion the number of perioperative ischemic events (p = 0.008) and combined perioperative complications (38.2 % vs. 14.3%; p = 0.006) was significantly higher in female than in male patients. Our study suggests that women with contralateral ICA stenosis or occlusion may have a significantly higher risk for perioperative CEA complications than other subgroups of CEA patients. This risk increase seems to be gender-specific and, if confirmed in larger prospective studies, may influence ICA stenosis therapy in the presence of a contralateral ICA stenosis/occlusion in female patients.     

Attentional blink modulation in a reaction time task: performance feedback,warning stimulus modality,and task difficulty

The present research investigated the effect of performance feedback on the modulation of the acoustic startle reflex in a Go/NoGo reaction time task. Experiment 1 (n = 120) crossed warning stimulus modality (acoustic, visual, and tactile) with the provision of feedback in a between subject design. Provision of performance feedback increased the number of errors committed and reduced reaction time, but did not affect blink modulation significantly. Attentional blink latency and magnitude modulation was larger during acoustic than during visual and larger during visual than during tactile warning stimuli. In comparison to control blinks, latency shortening was significant in all modality conditions whereas magnitude facilitation was not significant during tactile warning stimuli. Experiment 2 (n = 80) employed visual warning stimuli only and crossed the provision of feedback with task difficulty. Feedback and difficulty affected accuracy and reaction time. Whereas blink latency shortening was not affected, blink magnitude modulation was smallest in the Easy/No Feedback and the Difficult/Feedback conditions.     

Alanylation of teichoic acids protects Staphylococcus aureus against Toll-like receptor 2-dependent host defense in a mouse tissue cage infection model

Staphylococcus aureus is inherently resistant to cationic antimicrobial peptides because of alanylation of cell envelope teichoic acids. To test the effect of alanylated teichoic acids on virulence and host defense mediated by Toll-like receptor 2 (TLR2), wild-type (wt) S. aureus ATCC35556 (S.a.113) and its isogenic mutant expressing unalanylated teichoic acids (dlt(-)) were compared in a tissue cage infection model that used C57BL/6 wt and TLR2-deficient mice. The minimum infective doses (MID) to establish persistent infection with S.a.113 were 10(3) and 10(2) colony-forming units (cfu) in wt and TLR2(-/-) mice, respectively. The corresponding MID for dlt(-) were 5x105 and 10(3) cfu in wt and TLR2(-/-) mice, respectively. Both mouse strains showed bacterial-load-dependent inflammation with elevations in tumor necrosis factor, macrophage inflammatory protein 2, and leukocytes, with increasing proportions of dead cells. These findings indicate that alanylated teichoic acids contribute to virulence of S. aureus, and TLR2 mediates host defense, which partly targets alanylated teichoic acids.     

Activities of drug metabolizing enzymes in bovine colon epithelial cell cultures

The metabolic competence of cultured bovine colon epithelial cells was evaluated by determining activities of phase I and II enzymes in colonocytes cultured for different intervals (maximum of 10 days) compared with activities measured in freshly isolated cells. Cytochrome P450 1A1-associated 7-ethoxyresorufin O-deethylase (EROD) activity was detectable in freshly isolated colonocytes and in colon cells maintained in culture for up to 5 days. In contrast to liver samples, cytochrome P450 3A4-associated 7-benzyloxyresorufin O-debenzylase (BROD) activity was not detectable in bovine colon cells. Prostaglandin H synthase-mediated production of prostaglandin E₂ was found in freshly isolated and also in cultured colonocytes. Both isoenzymes (COX 1 and COX 2) were detected in cultured cells. To examine phase II metabolic potency, activities of N-acetyltransferases 1 and 2, of phenol and amino sulfotransferases, of glutathione S-transferases alpha, mu, pi and theta and of UDP-glucuronyltransferase were measured. N-Acetyltransferase (NAT) activity (substrate p-aminobenzoic acid, PABA, a diagnostic substrate for the human NAT-1 enzyme) was stable under culture conditions and during the observed culture period comparable to that of freshly isolated cells. In contrast, sulfamethazine, a specific substrate for NAT-2, was not acetylated, neither in bovine colon cells nor in bovine liver samples. Whereas activity of amino sulfotransferase (substrate 2-naphthylamine) decreased continuously during the entire culture period, the activity of phenol sulfotransferase (substrate 1-naphthol) decreased only slowly. Activity of total glutathione S-transferases (alpha, mu, and pi) (substrate 1-chloro-2,4-dinitrobenzene) decreased after 2 days in culture, but was stable during the following culture period. Activity of glutathione S-transferase theta (substrate epoxy-3-nitrophenoxypropane) changed during the culture period. At the beginning and the end (after 10 days) of the culture period maximum activity was measured. Activity of UDP-glucuronyltransferase increased during the culture period reaching a maximum after 7 days. The results show that cultured bovine epithelial colon cells express several enzyme activities required for the biotransformation of xenobiotics.     

Role of c-MET in upper aerodigestive malignancies--from biology to novel therapies.

Overactivation and defective downregulation of receptor tyrosine kinase (RTK) pathways have been implicated in human carcinogenesis. RTKs represent an important class of anticancer novel therapeutic target. Some RTKs are known to be protooncogenes that can mediate signal transduction, alteration of reactive oxygen species (ROS), cellular proliferation, cell motility and migration, apoptosis, and survival. c-MET is a unique RTK that regulates a wide variety of cellular functions. c-MET has been shown to be overexpressed or mutated in a variety of human malignancies. Stimulation of c-MET via its natural ligand hepatocyte growth factor/ scatter factor (HGF/SF) leads to a plethora of biological and biochemical effects in the cell. Activation of c-MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. This review summarizes the structure and functions of c-MET, with particular emphasis on its role in upper aerodigestive malignancies. The unique biological functions altered by c-MET and its mutations are discussed as well. Finally, c-MET, when mutated or overexpressed in malignant cells, serves as an important therapeutic target, and the most recent data with respect to its inhibition are also summarized in this review.     

Restraint use among nursing home residents: cross‐sectional study and prospective cohort study

Aims and objectives. To investigate (1) the prevalence of physical restraints and psychoactive medication, (2) newly administered physical restraints, frequency of application of the devices and frequency of psychoactive medication on demand during 12‐month follow‐up and (3) characteristics associated with restraint use in nursing homes. Background. High quality data on restraint use in German nursing homes are lacking so far. Such information is the basis for interventions to achieve a restraint‐free care. Design. Cross‐sectional study and prospective cohort study. Setting and subjects. Thirty nursing homes with 2367 residents in Hamburg, Germany. Methods. External investigators obtained prevalence of physical restraints by direct observation on three occasions on one day, psychoactive drugs were extracted from residents’ records and prospective data were documented by nurses. Results. Residents’ mean age was 86 years, 81% were female. Prevalence of residents with at least one physical restraint was 26·2% [95% confidence interval (CI) 21·3–31·1]. Centre prevalence ranged from 4·4 to 58·9%. Bedrails were most often used (in 24·5% of residents), fixed tables, belts and other restraints were rare. Prevalence of residents with at least one psychoactive drug was 52·4% (95% CI 48·7–56·1). The proportion of residents with at least one physical restraint after the first observation week of 26·3% (21·3–31·3) cumulated to 39·5% (33·3–45·7) at the end of follow‐up (10·4 SD 3·3 months). The relative frequency of observation days with at least one device ranged from 4·9–64·8% between centres. No characteristic was found to explain centre differences. Conclusions. The frequency of physical restraints and psychoactive drugs in German nursing homes is substantial. Pronounced centre variation suggests that standard care is possible without restraints. Relevance to clinical practice. Effective restraint minimisation approaches are urgently warranted. An evidence‐based guideline may overcome centre differences towards a restraint‐free nursing home care.