[Cerebral amyloid angiopathy associated with inflammation]. / Zerebrale Amyloidangiopathie assoziiert mit Inflammation.

Cerebral amyloid angiopathy (CAA) associated with inflammation is a rare form of a potentially reversible encephalopathy in a subgroup of patients with CAA. The cerebral amyloid deposition can in isolated cases induce an inflammation predominantly of the cerebral blood vessels and a multifocal edema of the cerebral white matter. The courses can occur as monophasic, relapsing remitting and primarily progressive forms. We present seven cases with different courses of the disease and give an overview of the pathophysiology, clinical aspects and treatment of the disease with reference to the current literature. The cases presented show a very different and often difficult differential diagnostic clinical picture and all showed a significant improvement under steroid medication without signs of recurrence of the disease during the course. The recognition and early consistent treatment of inflammatory forms of CAA with and without direct inflammatory involvement of vessels can be decisive for successful treatment.

Virtual staining of colon cancer tissue by label-free Raman micro-spectroscopy.

The great capability of the label-free classification of tissue via vibrational spectroscopy, like Raman or infrared imaging, is shown in numerous publications (review: Diem et al., J. Biophotonics, 2013, 6, 855-886). Herein, we present a new approach, virtual staining, that improves the Raman spectral histopathology (SHP) images of colorectal cancer tissue by combining the integrated Raman intensity image in the C-H stretching region (2800-3050 cm-1) with the pseudo-colour Raman image. This allows the display of fine structures such as the filamentous composition of muscle tissue. The morphology of the virtually stained images is in agreement with the gold standard in medical diagnosis, the haematoxylin-eosin staining. The virtual staining image also represents the whole biochemical fingerprint, and several tissue components including carcinoma were identified automatically with high sensitivity and specificity. For fast tissue classifications, a similar approach was applied on coherent anti-Stokes Raman scattering (CARS) spectral data that is faster and therefore potentially more suitable for clinical applications.

Quantitative assessment of growing hair counts, thickness and colour during and after treatments with a low-fluence, home-device laser: a randomized controlled trial.

BACKGROUND: At-home laser and intense pulsed-light hair removal continues to grow in popularity and availability. A relatively limited body of evidence is available on the course of hair growth during and after low-fluence laser usage. OBJECTIVES: To assess growing hair counts, thickness and colour quantitatively during and after cessation of low-fluence laser treatment. METHODS: Thirty-six women with skin phototypes I-IV and light to dark-brown axillary hairs were included. Entire axillary regions were randomized to zero or eight self-administered weekly treatments with an 810-nm home-use laser at 5·0-6·4 J cm(-2). Standardized clinical photographs were taken before each treatment and up to 3 months after the final treatment for computer-aided quantification of growing hair counts, thickness and colour. RESULTS: Thirty-two women completed the study protocol. During sustained treatment, there was a reduction in growing hair that reached a plateau of up to 59%, while remaining hairs became up to 38% thinner and 5% lighter (P < 0·001). The majority of subjects (77%) reported 'moderately' to 'much less hair' in treated than untreated axilla, and assessed remaining hairs as thinner and lighter (≥ 60%). After treatment cessation, hair growth gradually returned to baseline levels, and 3 months after the final treatment the count and thickness of actively growing hair exceeded pretreatment values by 29% and 7%, respectively (P ≤ 0·04). CONCLUSIONS: Sustained usage of low-fluence laser induced a stable reduction of growing hair counts, thickness and colour. The reduction was reversible and hairs regrew beyond baseline values after cessation of usage. Computer-aided image analysis was qualified for quantification of hair counts, thickness and colour after laser epilation.

Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas--a randomized clinical trial.

BACKGROUND: Photodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome. OBJECTIVES: To evaluate efficacy and safety of AFXL-mediated PDT (AFXL-PDT) compared with conventional PDT of high-risk nBCC. METHODS: Patients with histologically verified facial nBCC (n = 32) defined as high-risk tumours were included; diameter > 15 mm, tumours located in high-risk zones, or on severely sun-damaged skin. Tumours were debulked and patients randomized to either AFXL-PDT (n = 16) or PDT (n = 16). Fractional CO2 laser treatment was applied at 5% density and 1000 µm (80 mJ) ablation depth. MAL was applied under occlusion for 3 h and illuminated with a 633-nm light-emitting diode source, 37 J cm(-2) . Clinical assessments were performed at 3, 6, 9 and 12 months and biopsies were taken at 12 months. RESULTS: Clinical cure rates at 3 months were 100% (16 of 16 AFXL-PDT) and 88% (14 of 16 PDT, P = 0·484). Recurrences tended to occur later and in lower numbers after AFXL-PDT at 6, 9 and 12 months (6%, 19%, 19%) than PDT (25%, 38%, 44%) (P = 0·114). Histology at 12 months documented equal tumour clearance after AFXL-PDT (63%, 10 of 16) and PDT (56%, 9 of 16). Cosmetic outcomes were highly satisfactory after both treatments (P > 0·090). CONCLUSIONS: Long-term efficacy was similar after PDT and AFXL-PDT with a trend for a favourable short-term cure rate after AFXL-PDT. AFXL-PDT needs further refinement for nBCC and at present is not recommended over PDT.

Are we burying our heads in the sand? Preventing small bowel obstruction from the V-loc® suture in laparoscopic ventral rectopexy.

AIM: There have been increasing reports in the literature highlighting the complication of V-loc® associated small bowel obstruction in patients after laparoscopic ventral rectopexy. METHODS AND RESULTS: Using clinical and experimental evidence, we demonstrate that bowel obstruction from the V-loc® following laparoscopic ventral rectopexy will still occur despite the technical recommendations to bury or cut its barbed end flush. CONCLUSION: The risk of bowel obstruction from the V-loc® following laparoscopic ventral rectopexy is not negated by burying or cutting its barbed end flush. We have proposed its pathogenesis to refute commonly held assumptions about its prevention.

Clinical condition of cull sows before and after transport to slaughter - Effects of journey duration and a stationary period.

This factorial study was part of a project examining potential welfare challenges for cull sows in the pre-slaughter logistic chain, and examined effects of journey duration and presence of a longer pre-planned stop half-way during journeys on their post-transport clinical condition. The sows were transported 4, 6 or 8 h under conditions modelling typical Danish practice. In addition, across 49 journeys, effects of temperature inside the vehicle and time spent waiting before unloading at the slaughterhouse were examined. The results confirmed the findings of our earlier observational study, showing that the clinical conditions of cull sows deteriorated during transport, but also that none of the 578 sows arrived at the slaughterhouse in a condition that would have rendered them unfit for transport. A complex picture was found in relation to the clinical variables affected by journey duration, involvement of a longer pre-planned stop, and/or time spent waiting before unloading. This suggests that several factors contribute to the deterioration of the clinical condition of sows, but not consistently or as unequivocal causal factors, at least within the studied journey durations. Based on the deterioration in their clinical condition, especially for variables associated with heat stress and aggression, and knowing that the amount of time the sows are exposed to hazards such as aggressive pen mates, high temperatures and/or moving vehicles is dependent on the journey duration, keeping journeys as short as possible will most likely be advantageous. Future studies should also focus on how to optimise the social and microclimatic environment.

Surgical outcomes in steroid refractory acute severe ulcerative colitis: the impact of rescue therapy.

AIM: The advent of rescue medical therapy (cyclosporin or infliximab) and laparoscopic surgery has shifted the paradigm in managing steroid refractory acute severe ulcerative colitis (ASUC). We investigated prospectively the impact of rescue therapy on timing and postoperative complications of urgent colectomy and subsequent restorative surgery for steroid refractory ASUC. METHOD: All consecutive presentations of steroid refractory ASUC at the Royal Brisbane Hospital (1996-2009) were entered in the study. Data collated included demographics, clinical and laboratory parameters on admission, medical therapy and operative and postoperative details. Steroid refractory ASUC patients undergoing immediate colectomy were compared with those failing rescue therapy and requiring same admission colectomy. RESULTS: Of 108 steroid refractory ASUC presentations, 19 (18%) received intravenous steroids only and proceeded directly to colectomy. Rescue medical therapy was instituted in 89 (82%) patients with 30 (34%) failing to respond and proceeding to colectomy. There was no significant difference in the median time from admission to colectomy for rescue therapy compared with steroid-only cases (12 vs 10 days, P = 0.70) or 30-day complication rates (27%vs 47%, P = 0.22). The interval from colectomy to a subsequent restorative procedure was significantly longer for patients who failed rescue therapy (12 vs 5 months, P = 0.02). Furthermore 30-day complications following pouch surgery were significantly higher in patients who failed rescue therapy (32%vs 0%, P = 0.01). CONCLUSION: Rescue therapy in steroid refractory ASUC is not related to delay in urgent colectomy or increased post-colectomy complications.

Safety and efficacy of repetitive adenovirus-mediated transfer of CFTR cDNA to airway epithelia of primates and cotton rats.

Gene therapy for cystic fibrosis (CF) will require the safe transfer of CFTR cDNA to airway epithelia in vivo. We showed previously that a recombinant adenovirus, Ad2/CFTR-1, expresses CFTR in vitro. As adenovirus rarely integrates, treatment will require repeated vector administration. We applied Ad2/CFTR-1 to intrapulmonary airway epithelia of cotton rats and nasal epithelia of Rhesus monkeys. In both species we detected CFTR mRNA and protein after repeated administration and in monkeys, protein was detected six weeks after repeat administration. The vector did not replicate and was rapidly cleared. Despite an antibody response, there was no evidence of a local or systemic inflammatory response after repeat administration. These data indicate that repetitive administration of Ad2/CFTR-1 is both safe and efficacious.

Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial.

BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is effective for thin actinic keratoses (AKs) in field-cancerized skin. Ablative fractional laser resurfacing (AFXL) creates vertical channels that facilitate MAL uptake and may improve PDT efficacy. OBJECTIVES: To evaluate efficacy and safety of AFXL-assisted PDT (AFXL-PDT) compared with conventional PDT in field-directed treatment of AK. METHODS: Fifteen patients with a total of 212 AKs (severity grade I-III) in field-cancerized skin of the face and scalp were randomized to one treatment with PDT and one treatment with AFXL-PDT in two symmetrical areas. Following curettage of both treatment areas, AFXL was applied to one area using 10 mJ per pulse, 0·12 mm spot, 5% density, single pulse (UltraPulse(®), DeepFx handpiece; Lumenis Inc., Santa Clara, CA, U.S.A.). MAL cream was then applied under occlusion for 3 h and illuminated with red light-emitting diode light at 37 J cm(-2). Fluorescence photography quantified protoporphyrin IX (PpIX) before and after illumination. RESULTS: At 3-month follow-up, AFXL-PDT was significantly more effective than PDT for all AK grades. Complete lesion response of grade II-III AK was 88% after AFXL-PDT compared with 59% after PDT (P = 0·02). In grade I AK, 100% of lesions cleared after AFXL-PDT compared with 80% after PDT (P = 0·04). AFXL-PDT-treated skin responded with significantly fewer new AK lesions (AFXL-PDT n = 3, PDT n = 11; P = 0·04) and more improved photoageing (moderate vs. minor improvement, P = 0·007) than PDT-treated skin. Pain scores during illumination (6·5 vs. 5·4; P = 0·02), erythema and crusting were more intense, and long-term pigmentary changes more frequent from AFXL-PDT than PDT (P = not significant). PpIX fluorescence was higher in AFXL-pretreated skin [7528 vs. 12,816 arbitrary units (AU); P = 0·003] and photobleached to equal intensities after illumination (AFXL-PDT 595 AU, PDT 454 AU; P = 0·59). CONCLUSIONS: AFXL-PDT is more effective than conventional PDT for treatment of AK in field-cancerized skin.

The ideal ileal-pouch design: a long-term randomized control trial of J- vs W-pouch construction.

BACKGROUND: The IPAA has become established as the preferred technique for restoring intestinal continuity postproctocolectomy. The ideal pouch design has not been established. W-pouches may give better functional results owing to increased volume, whereas the J-pouch's advantage is its straightforward construction. We report short- and long-term results of an randomized control trial designed to establish the ideal pouch. DESIGN: Ninety-four patients were randomly assigned to J- and W-pouches (49:45) and assessed at 1 and 8.7 years postoperatively. Assessment was questionnaire based and designed to assess pouch function and patient quality of life. RESULTS: Eighty-five percent of patients were followed up at 1 year, and 68% were followed up at 8.7 years. At 1 year, there was a significant difference in 24-hour bowel movement frequency J- vs W-pouches 7 vs 5(p < 0.001) and in daytime frequency J- vs W-pouches 6 vs 4 (p < 0.001), with no difference in nocturnal function. At 9-year follow-up, function had equilibrated between the 2 groups: 24-hour bowel movement frequency J- vs W-pouches 6.5 vs 6 (p = 0.36), daytime frequency 5.5 vs 5 (p = 0.233), and nocturnal function 1 vs 1 (p = 0.987). Mean operating time of J- and W-pouches was 195 and 215 minutes (p < 0.05). All other parameters, pad usage, urgency, incontinence, and quality of life, did not differ significantly between groups. CONCLUSION: These data demonstrate that the theoretical functional advantage conferred on the W-pouch by its greater volume exists only in the short term and is of little consequence to patients' long-term quality of life. This advantage is attenuated as the pouches mature, resulting in no disparity in pouch function. This, combined with the more consistent, efficient, and easily taught construction of the J-pouch, should conclusively establish it as the optimum ileal-pouch design.

A systematic review of light-based home-use devices for hair removal and considerations on human safety.

BACKGROUND: Hair removal with professional light-based devices is established as an effective, mainstream treatment. The field of optical home-based hair removal is evolving and movement from control by physicians into hands of consumers warrants understanding efficacy and human safety. OBJECTIVES: To systematically review and evaluate the efficacy and human safety of currently available home-based optical hair removal devices. METHODS: A comprehensive Pub Med literature search was conducted which systematically identified publications of relevance. Prospective clinical trials were included whether controlled, uncontrolled or randomized and with a sample size of at least 10 individuals. RESULTS: We identified a total of seven studies: one controlled (CT) and six uncontrolled trials (UCTs). No randomized controlled trials (RCT) were recognized. The best evidence was found for IPL (intense pulsed light) (three devices, one CT, five UCTs) and limited evidence for laser devices (one diode laser, one UCT). Most studies evaluated short-term hair reduction up to 3 and 6 months following light exposure at different body sites. Hair reduction percentages ranged from 6% to 72% after repetitive treatments. The most frequently reported side-effect was erythema, but oedema, blistering, crusting and pigment changes were also reported. Theoretical concerns about ocular damage and paradoxical hair growth have not been reported in any of the studies reviewed. CONCLUSIONS: Available evidence from prospective, uncontrolled clinical trials indicates short-term hair removal efficacy of currently available home-use light-based hair removal devices. Additional controlled trials will be helpful to substantiate the efficacy and to better predict the incidence of adverse events associated with optical home-use hair removal.

Adolescence alcohol exposure impairs fear extinction and alters medial prefrontal cortex plasticity.

After experiencing a traumatic event people often turn to alcohol to cope with symptoms. In those with post-traumatic stress disorder (PTSD) and a co-occurring alcohol use disorder (AUD), PTSD symptoms can worsen, suggesting that alcohol changes how traumatic memory is expressed. The objective of this series of experiments is to identify how alcohol drinking (EtOH), following cued fear conditioning and extinction, impacts fear expression in mice. Molecular (activity-regulated cytoskeleton-associated protein, Arc/arg3.1) and structural (dendrite and spine morphometry) markers of neuronal plasticity were measured following remote extinction retrieval. Mouse age (adolescent and adult) and sex were included as interacting variables in a full factorial design. Females drank more EtOH than males and adolescents drank more EtOH than adults. Adolescent females escalated EtOH intake across drinking days. Adolescent drinkers exhibited more conditioned freezing during extinction retrieval, an effect that persisted for at least 20 days. Heightened cued freezing in the adolescent group was associated with greater Arc/arg3.1 expression in layer (L) 2/3 prelimbic (PL) cortex, greater spine density, and reduced basal dendrite complexity. In adults, drinking was associated with reduced L2/3 infralimbic (IL) Arc expression but no behavioral differences. Few sex interactions were uncovered throughout. Overall, these data identify prolonged age-related differences in alcohol-induced fear extinction impairment and medial prefrontal cortex neuroadaptations.

Fast and direct measurements of the electrical properties of graphene using micro four-point probes.

We present measurements of the electronic properties of graphene using a repositionable micro four-point probe system, which we show here to have unique advantages over measurements made on lithographically defined devices; namely speed, simplicity and lack of a need to pattern graphene. Measurements are performed in ambient, vacuum and controlled environmental conditions using an environmental scanning electron microscope (SEM). The results are comparable to previous results for microcleaved graphene on silicon dioxide (SiO(2)). We observe a pronounced hysteresis of the charge neutrality point, dependent on the sweep rate of the gate voltage; and environmental measurements provide insight into the sensor application prospects of graphene. The method offers a fast, local and non-destructive technique for electronic measurements on graphene, which can be positioned freely on a graphene flake.

Detection of meticillin-resistant Staphylococcus aureus and carbapenemase-producing Enterobacteriaceae in Danish emergency departments - evaluation of national screening guidelines.

BACKGROUND: Multi-resistant bacteria (MRB) are an emerging problem. Early identification of patients colonized with MRB is mandatory to avoid in-hospital transmission and to target antibiotic treatment. Since most patients pass through specialized emergency departments (EDs), these departments are crucial in early identification. The Danish National Board of Health (DNBH) has developed exposure-based targeted screening tools to identify and isolate carriers of meticillin-resistant Staphylococcus aureus (MRSA) and carbapenemase-producing Enterobacteriaceae (CPE). AIM: To assess the national screening tools for detection of MRSA and CPE carriage in a cohort of acute patients. The objectives were to investigate: (i) if the colonized patients were detected; and (ii) if the colonized patients were isolated. METHODS: This was a multi-centre cross-sectional survey of adults visiting EDs. The patients answered the DNBH questions, and swabs were taken from the nose, throat and rectum. The collected samples were examined for MRSA and CPE. Screening performances were calculated. FINDINGS: Of the 5117 included patients, 16 were colonized with MRSA and four were colonized with CPE. The MRSA screening tool had sensitivity of 50% [95% confidence interval (CI) 25-75%] for carrier detection and 25% (95% CI 7-52%) for carrier isolation. The CPE screening tool had sensitivity of 25% (95% CI 1-81%) and none of the CPE carriers were isolated. CONCLUSION: The national screening tools were of limited use as the majority of MRSA and CPE carriers passed unidentified through the EDs, and many patients were isolated unnecessarily.

The effect of thymidine on the duration of G1 in Chinese hamster cells.

The generation time of a Chinese hamster cell line was varied by the use of different lots of sera in the culture media. Analysis of the division waves following thymidine synchronization showed that lengthening of the generation time was a result of an increase in duration of the G(1) phase and that thymidine treatment reduced the duration of G(1) back to its minimum value.

DNA constancy in heteroploidy and the stem line theory of tumors.

Cellular DNA was measured by high-speed flow microfluorometry in mammalian diploid and heteroploid cell populations stained by the fluorescent Feulgen procedure. Heteroploid cells with elevated modal chromosome number showed the expected increase in modal DNA content. However, the variability of DNA content was the same in diploid and heteroploid cell populations despite the large variability of chromosome number in the latter populations. This suggests that heteroploidy may include defects in the chromosomal condensation and kinetochore development systems.

Novel Plexor SNP genotyping technology: comparisons with TaqMan and homogenous MassEXTEND MALDI-TOF mass spectrometry.

Analysis of SNPs for association, linkage, haplotype, and pharmacogenetic studies has led to a dramatic increase in the number and evolution of medium- to high-throughput genotyping technologies. This study introduces Plexor as a new method for medium-throughput (single SNP) genotyping. We compare this fluorescent-based chemistry for call rate, accuracy, affordability, throughput, and overall efficiency against two commonly used technologies. These include fluorescent-based TaqMan allelic discrimination for single SNP analysis (medium-throughput) and the homogenous MassEXTEND (hME) chemistry using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for multiple SNP analysis (high-throughput). Analysis of 11 SNPs, including all six possible nucleotide substitutions, showed Plexor to be highly comparable for both call rate (94.7%) and accuracy (99.2%) to the TaqMan (94.6% and 99.8%, respectively) and hME (91.9% and 98.1%, respectively) chemistries. We demonstrate that this novel method is an efficient, cost-effective alternative to TaqMan genotyping commonly used in diagnostic settings.

Location and characterization of two widely separated glucocorticoid response elements in the phosphoenolpyruvate carboxykinase gene.

Chimeric genes were constructed by fusion of various regions of the 5'-flanking sequence from the phosphoenolpyruvate carboxykinase (GTP) (PEPCK) gene to the chloramphenicol acetyltransferase-coding sequence and to simian virus 40 splice and polyadenylation sequences. These were used to demonstrate that two glucocorticoid regulatory elements (GREs) combine to confer glucocorticoid responsiveness upon the PEPCK gene in H4IIE hepatoma cells. Both elements, a distal one whose 5' boundary is located between -1264 and -1111 base pairs and a proximal one located between -468 and -420 base pairs relative to the transcription initiation site, act independently, in various positions and orientations, and upon the heterologous thymidine kinase promoter. Each element accounts for half of the maximal response of the chimeric genes. Therefore, two widely separated enhancerlike elements contribute equally to the response of the PEPCK gene to glucocorticoid hormones. Neither of the PEPCK GREs contains the TGTTCT consensus sequence associated with most other GREs.

The effect of breathing an ambient low-density, hyperoxic gas on the perceived effort of breathing and maximal performance of exercise in well-trained athletes.

BACKGROUND: The role of the perception of breathing effort in the regulation of performance of maximal exercise remains unclear. AIMS: To determine whether the perceived effort of ventilation is altered through substituting a less dense gas for normal ambient air and whether this substitution affects performance of maximal incremental exercise in trained athletes. METHODS: Eight highly trained cyclists (mean SD) maximal oxygen consumption (VO(2)max) = 69.9 (7.9) (mlO(2)/kg/min) performed two randomised maximal tests in a hyperbaric chamber breathing ambient air composed of either 35% O(2)/65% N(2) (nitrox) or 35% O(2)/65% He (heliox). A ramp protocol was used in which power output was incremented at 0.5 W/s. The trials were separated by at least 48 h. The perceived effort of breathing was obtained via Borg Category Ratio Scales at 3-min intervals and at fatigue. Oxygen consumption (VO(2)) and minute ventilation (V(E)) were monitored continuously. RESULTS: Breathing heliox did not change the sensation of dyspnoea: there were no differences between trials for the Borg scales at any time point. Exercise performance was not different between the nitrox and heliox trials (peak power output = 451 (58) and 453 (56) W), nor was VO(2)max (4.96 (0.61) and 4.88 (0.65) l/min) or maximal V(E) (157 (24) and 163 (22) l/min). Between-trial variability in peak power output was less than either VO(2)max or maximal V(E). CONCLUSION: Breathing a less dense gas does not improve maximal performance of exercise or reduce the perception of breathing effort in highly trained athletes, although an attenuated submaximal tidal volume and V(E) with a concomitant reduction in VO(2) suggests an improved gas exchange and reduced O(2) cost of ventilation when breathing heliox.