Overcoming barriers to the mobilisation of patients in an intensive care unit.

We conducted a quality improvement project aimed at increasing the frequency of mobilisation in our ICU. We designed a four-part quality improvement project comprising: an audit documenting the baseline frequency of mobilisation; a staff survey evaluating perceptions of the barriers to mobilisation; identification of barriers that were amenable to change and implementation of strategies to address these; and a follow-up audit to determine their effectiveness. The setting was a tertiary care, urban, public hospital ICU in South Australia. All patients admitted to the ICU during the two audit periods were included in the audits, while all permanent/semi-permanent ICU staff were eligible for inclusion in the staff survey. We found that patient- and institution-related factors had the greatest impact on the mobilisation of patients in our ICU. Barriers identified as being amenable to change included insufficient staff education about the benefits of mobilisation, poor interdisciplinary communication and lack of leadership regarding mobilisation. Various strategies were implemented to address these barriers over a three-month period. Multivariable analyses showed that three out of four mobility outcomes did not significantly change between the baseline and follow-up audits, with a significant difference in favour of the baseline audit found for the fourth mobility outcome (maximum level of mobility). We concluded that implementing relatively simple measures to improve staff education, interdisciplinary communication and leadership regarding early progressive mobilisation was ineffective at improving mobility outcomes for patients in a large tertiary-level Australian ICU. Other strategies, such as changing sedation practices and/or increasing staffing, may be required to improve mobility outcomes of these patients.

An APT investigation of an amorphous Cr-B-C thin film.

A magnetron sputtered amorphous Cr-B-C thin film was investigated by means of atom probe tomography (APT). The film is constituted of two phases; a Cr-rich phase present as a few nanometer large regions embedded in a Cr-poor phase (tissue phase). The Cr-rich regions form columnar chains oriented parallel to the growth direction of the film. It was found that the Cr-rich regions have a higher B:C ratio than the Cr-poor regions. The composition of the phases was determined as approximately 35Cr-33B-30C and 15Cr-40B-42C (at%), respectively. The results suggest that this type of nanocomposite films has a more complex structure than previously anticipated, which may have an importance for the mechanical and electrical properties.

Blind deconvolution of time-of-flight mass spectra from atom probe tomography.

A major source of uncertainty in compositional measurements in atom probe tomography stems from the uncertainties of assigning peaks or parts of peaks in the mass spectrum to their correct identities. In particular, peak overlap is a limiting factor, whereas an ideal mass spectrum would have peaks at their correct positions with zero broadening. Here, we report a method to deconvolute the experimental mass spectrum into such an ideal spectrum and a system function describing the peak broadening introduced by the field evaporation and detection of each ion. By making the assumption of a linear and time-invariant behavior, a system of equations is derived that describes the peak shape and peak intensities. The model is fitted to the observed spectrum by minimizing the squared residuals, regularized by the maximum entropy method. For synthetic data perfectly obeying the assumptions, the method recovered peak intensities to within ±0.33 at%. The application of this model to experimental APT data is exemplified with Fe-Cr data. Knowledge of the peak shape opens up several new possibilities, not just for better overall compositional determination, but, e.g., for the estimation of errors of ranging due to peak overlap or peak separation constrained by isotope abundances.

Atom probe tomography of Ni-base superalloys Allvac 718Plus and Alloy 718.

Atom probe tomography (APT) allows near atomic scale compositional- and morphological studies of, e.g. matrix, precipitates and interfaces in a wide range of materials. In this work two Ni-base superalloys with similar compositions, Alloy 718 and its derivative Allvac 718Plus, are subject for investigation with special emphasis on the latter alloy. The structural and chemical nuances of these alloys are important for their properties. Of special interest are grain boundaries as their structure and chemistry are important for the materials' ability to resist rapid environmentally induced crack propagation. APT has proved to be suitable for analyses of these types of alloys using voltage pulsed APT. However, for investigations of specimens containing grain boundaries and other interfaces the risk for early specimen fracture is high. Analyses using laser pulsing impose lower electrical field on the specimen thereby significantly increasing the success rate of investigations. Here, the effect of laser pulsing was studied and the derived appropriate acquisition parameters were then applied for microstructural studies, from which initial results are shown. Furthermore, the influence of the higher evaporation field experienced by the hardening γ' Ni(3)(Al,Nb) precipitates on the obtained results is discussed.

Quantitative atom probe analysis of carbides.

Compared to atom probe analysis of metallic materials, the analysis of carbide phases results in an enhanced formation of molecular ions and multiple events. In addition, many multiple events appear to consist of two or more ions originating from adjacent sites in the material. Due to limitations of the ion detectors measurements generally underestimate the carbon concentration. Analyses using laser-pulsed atom probe tomography have been performed on SiC, WC, Ti(C,N) and Ti(2)AlC grains in different materials as well as on large M(23)C(6) precipitates in steel. Using standard evaluation methods, the obtained carbon concentration was 6-24% lower than expected from the known stoichiometry. The results improved remarkably by using only the (13)C isotope, and calculating the concentration of (12)C from the natural isotope abundance. This confirms that the main reason for obtaining a too low carbon concentration is the dead time of the detector, mainly affecting carbon since it is more frequently evaporated as multiple ions. In the case of Ti(C,N) and Ti(2)AlC an additional difficulty arises from the overlap between C(2)(+), C(4)(2+) and Ti(2+) at the mass-to-charge 24 Da.

Using atom probe tomography to analyse MAX-phase materials.

Ti(2)AlC belongs to an interesting group of materials with both metallic and ceramic properties. This material is highly attractive as a candidate for corrosion resistant coatings. The process of fabrication of such coatings is in the investigation stage only and the detailed knowledge of the structure and chemistry of the produced coatings is important for optimisation of their properties. In this work the applicability of atom probe tomography for investigation of both Ti(2)AlC bulk materials and coatings was tested. We show that for the first time, Ti(2)AlC has successfully been analysed using laser pulsing mode in a local electrode atom probe and the results from analysis of both bulk Ti(2)AlC and Ti(2)AlC based spray deposited coatings are presented. It appears that, in this particular material system, it is difficult to obtain the accurate stoichiometry. This is due to the loss of detection because of unavoidable multiple events and due to the peak overlaps present. Methods of how to approach these problems are discussed.

The timing and achievement of mobility skills during SCI rehabilitation.

STUDY DESIGN: Retrospective, observational study, with consecutive sampling. OBJECTIVES: To document the frequency and time frames for the achievement of independence in mobility skills for people undergoing rehabilitation following spinal cord injury (SCI). SETTING: The South Australian Spinal Cord Injury Service, Hampstead Rehabilitation Centre, Adelaide, Australia. METHODS: Retrospective data collection from a purpose-designed form. The achievement of independence in nine functional mobility skills, and time lines for this, were documented for people with a new SCI undergoing rehabilitation. Data from 152 participants were analyzed. RESULTS: Of the nine mobility-based goals evaluated, the one most likely to be achieved was sitting on the edge of the bed and the least likely was gait. Time taken to achieve the skills varied from 4 to 10 weeks on average and reflected the degree of difficulty. CONCLUSION: The frequency and time frames to achieve independence in mobility skills documented in this study will be useful when goal setting in a post-acute SCI rehabilitation setting.

Physiotherapy for adult patients with critical illness: recommendations of the European Respiratory Society and European Society of Intensive Care Medicine Task Force on Physiotherapy for Critically Ill Patients.

The Task Force reviewed and discussed the available literature on the effectiveness of physiotherapy for acute and chronic critically ill adult patients. Evidence from randomized controlled trials or meta-analyses was limited and most of the recommendations were level C (evidence from uncontrolled or nonrandomized trials, or from observational studies) and D (expert opinion). However, the following evidence-based targets for physiotherapy were identified: deconditioning, impaired airway clearance, atelectasis, intubation avoidance, and weaning failure. Discrepancies and lack of data on the efficacy of physiotherapy in clinical trials support the need to identify guidelines for physiotherapy assessments, in particular to identify patient characteristics that enable treatments to be prescribed and modified on an individual basis. There is a need to standardize pathways for clinical decision-making and education, to define the professional profile of physiotherapists, and increase the awareness of the benefits of prevention and treatment of immobility and deconditioning for critically ill adult patients.

The sensitivity of three commonly used outcome measures to detect change amongst patients receiving inpatient rehabilitation following stroke.

OBJECTIVE: To investigate the sensitivity of three commonly used functional outcome measures to detect change over time in subjects receiving inpatient rehabilitation post stroke. DESIGN: Subjects were assessed within one week of admission and one week of discharge from an inpatient rehabilitation facility. Several parameters of sensitivity were calculated, including floor and ceiling effects, the percentage of subjects showing no change and the effect size of the change between admission and discharge. SETTING: The medical rehabilitation ward of an inpatient rehabilitation facility. SUBJECTS: Seventy-eight subjects receiving inpatient rehabilitation following a first or recurrent stroke. MEASURES: Five-metre walk, comfortable pace (gait speed), the Berg Balance Scale and the Motor Assessment Scale. RESULTS: Sixty-one subjects had complete admission and discharge data. Gait speed and the Berg Balance Scale were both sensitive to change and demonstrated large effect sizes. The Motor Assessment Scale item five also showed a large effect size and was able to detect change amongst lower functioning subjects. The other items of the Motor Assessment Scale were less useful, in particular, the effect sizes for upper extremity change scores were small (d=0.36-0.5) and the majority of subjects (44.3-63.9%) showed no change over time on these measures. CONCLUSION: Gait speed, the Berg Balance Scale and the Motor Assessment Scale item five were sensitive to change over time in this sample.

A comparative quantitative analysis of laminin-5 in the basement membrane of normal, hyperplastic, and malignant oral mucosa by confocal immunofluorescence imaging.

Laminin-5 (Ln-5) is a heterotrimeric basement membrane (BM) molecule (alpha3beta3gamma2). It is a principal protein constituent of the anchoring filaments, which connect the BM with the hemidesmosomes of the basal keratinocytes and possess a crucial function in keratinocyte adhesion. Confocal immunofluorescence imaging is introduced for a quantitative evaluation of the Ln-5 content in the BM of oral squamous epithelium. The BM of normal oral mucosa was used as a reference (100%) for comparative analysis and showed a nearly uniform Ln-5 immunofluorescence intensity (99-100%). In all hyperplastic lesions of oral mucosa, the Ln-5 immunofluorescence intensity was increased (107-141%). The increased Ln-5 content in the BM of hyperplastic lesions suggests an increased keratinocyte-BM adhesion, possibly resulting in a higher stability of the oral mucosa. In contrast, in the oral squamous cell carcinoma (OSCC) invasive front, the remaining BM segments were characterized by a decrease in Ln-5 immunofluorescence intensity (35-74%). A stronger decrease of Ln-5-linked kerationocyte-BM adhesion correlates with a higher tumor grade. Because in central areas of carcinoma BM segments with a normal Ln-5 content could be demonstrated, the fundamental Ln-5 diminution in BM segments of the invasive front should be considered as an invasion-associated phenomenon.

The association between tumour progression and vascularity in myxofibrosarcoma and myxoid/round cell liposarcoma.

Angiogenesis is an important factor in the morphological progression and metastasis of many solid tumours. We studied two homogeneous series of myxofibrosarcoma (MFS) and myxoid/round liposarcoma (MRLS), characterised by distinct vascular patterns and correlated the intratumoral microvessel density (IMD) with morphologic progression in both types of sarcoma. In our study, 43 cases of MFS and 42 cases of MRLS were graded according to established diagnostic criteria. For evaluation of IMD, representative sections were stained immunohistochemically for CD31. After selection of "neovascular hot spots", IMD was calculated by measuring the endothelial surface within twenty 200x fields in relation to the total analysed area. In addition to the correlation of IMD with histological grades of malignancy, a correlation of IMD with the inflammatory infiltrate in MFS was done. To determine whether vascular endothelial growth factor (VEGF) and its receptors, KDR and flt-1, may play a role in the progression of both types of sarcomas, we used mRNA in situ hybridisation (ISH) to study VEGF, KDR and flt-1 expression in selected cases. In addition, the expression of thrombospondin-1, which has been reported to inhibit angiogenesis, and of collagen type I was studied using mRNA ISH. Cases of MFS varied histologically from hypocellular, mainly myxoid, neoplasms (low-grade malignant, 18 cases) to intermediate-grade malignant lesions with increased cellularity and mitotic activity (13 cases), and high-grade malignant cases with marked pleomorphism, high proliferative activity and areas of necrosis in many cases (12 cases). Cases of purely low-grade myxoid liposarcoma (16 cases) were characterised by low-cellularity, mucin pooling and plexiform vasculature. In combined MRLS, these hypocellular areas were admixed with hypercellular, round cell areas (5-80% of the analysed tumour area; 23 cases), and in round cell liposarcoma (three cases) rounded tumour cells predominated (>80% of the analysed tumour area). The average IMD in intermediate and high-grade malignant MFS (4.03 and 4.09, respectively) was significantly higher than in low-grade malignant MFS (2.73). Correlation of vascularity with the inflammatory infiltrate in MFS showed increased IMD only in cases with abundant neutrophils; most of these cases were high-grade malignant neoplasms. In contrast, no statistical correlation between morphological progression and IMD was seen in myxoid liposarcoma (6.08), MRLS (6.57) and round cell liposarcoma (4.07). VEGF mRNA was expressed by tumour cells in all histological grades of MFS and MRLS. VEGF receptor mRNA was weakly expressed by endothelia of newly formed blood vessels in both entities. Interestingly, tumour cells of all analysed cases of MFS strongly expressed collagen type I and thrombospondin-1, while these proteins were not detected in tumour cells of MRLS. In conclusion, morphologic tumour progression in MFS is associated with increased IMD, whereas, in MRLS, no such correlation is seen. Whereas VEGF and VEGF receptor mRNA were expressed in both entities, a characteristic expression profile of collagen type I and thrombospondin-1 in MFS emerged. Further studies are necessary to correlate vascularity and clinical course in MFS and MRLS.

Manual hyperinflation--effects on respiratory parameters.

BACKGROUND AND PURPOSE: Manual hyperinflation (MH) of the lungs is commonly used by physiotherapists in the treatment of intubated mechanically ventilated patients with the aim of increasing alveolar oxygenation, reversing atelectasis or mobilizing pulmonary secretions. However, the efficacy of MH, used in isolation, has not been clearly established. METHOD: This randomized, controlled trial investigated the effects of MH on lung compliance (CL), the arterial oxygen to fraction of inspired oxygen ratio (PaO2:FIO2) and the alveolar-arterial oxygen tension difference (A-a)PO2 in 100 medically stable, mechanically ventilated subjects who had undergone coronary artery surgery (CAS). Post-CAS subjects were used for this study as they constitute a large, homogeneous and accessible group. Subjects were randomized to either a control group (non-MH group) or to a treatment group (MH group) which received MH within four hours of surgery. RESULTS: After four minutes of MH there were significant improvements in CL, PaO2:FIO2 and (A-a)PO2 with values remaining above baseline measures at 60 min post-intervention. The mean improvement in CL was 6 ml/cmH2O (approximately 15%), 56 mmHg for PaO2:FIO2 (approximately 17%) and 29 mmHg for (A-a)PO2 (approximately 17%) immediately post-intervention. No significant changes in mean CL, PaO2:FIO2 or (A-a)PO2 were seen in the non-MH group. CONCLUSIONS: MH performed in the stable ventilated patient significantly increased CL and PaO2:FIO2 and decreased (A-a)PO2, but the clinical significance of this improvement is unclear. Further investigations are required to validate the findings of this study as well as to determine the therapeutic value of MH on patient outcome.

Expression of LFA-1 (CD11a/CD18) and ICAM-1 (CD54) in an animal model of renal interstitial fibrosis induced by unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) has been used as an experimental model to induce tubulointerstitial damage and interstitial fibrosis. UUO is characterized by cellular proliferation, accumulation of inflammatory cells, and subsequent replacement of renal parenchyma by fibrous tissue. The influx of inflammatory cells into the renal interstitium is mediated by adhesion molecules. In this study, the development of fibrosis in the UUO model of the rat was examined and its relation to the time course of LFA-1 and ICAM-1 expression was assessed by immunohistochemistry. An increase in interstitial connective tissue was detected on day 10 after UUO, with a maximum on day 35. After unilateral ureteral obstruction, LFA-1 was prominently expressed in interstitial infiltrates, and to a lesser degree in glomerular areas. An initial increase in LFA-1-positive cells was noted already on day 10, with a maximum on day 20 and a decline on day 25. During the time course of 35 days after UUO, we observed an increase in ICAM-1 expression in the vascular endothelium, in tubular epithelium and in interstitial areas. This study shows that LFA-1 expression and ICAM-1 expression are concordant and that this process is associated with increasing interstitial fibrosis. ICAM-1 interstitial tissue may facilitate the homing and persistence of an interstitial infiltrate by ICAM-1/LFA-1 interactions, thereby preceding the development of renal interstitial fibrosis.

123I-antileukoproteinase scintigraphy reveals microscopic cartilage alterations in the contralateral knee joint of rats with "monarticular" antigen-induced arthritis.

OBJECTIVE: To assess the involvement of the contralateral knee joint in monarticular antigen-induced arthritis (AIA) by scintigraphy with the cationic (pI >10), 123I-labeled, serine proteinase inhibitor antileukoproteinase (123I-ALP) and to compare the scintigraphic findings with those of radiography and high-resolution ex vivo magnetic resonance imaging (MRI). METHODS: Lewis rats with chronic AIA were examined 2.5 months following arthritis induction (injection of 500 microg of methylated bovine serum albumin/saline into the ipsilateral [arthritic] knee joint and injection of phosphate buffered saline into the contralateral knee joint following systemic immunization). 123I-ALP was injected intravenously into normal rats (n = 4) or rats with AIA (n = 6). The ipsilateral and contralateral knee joints and both ankles were examined by scintigraphy and radiography. Joint cartilage was examined by high-resolution ex vivo MRI, histopathology, and measurement of tissue radioactivity. RESULTS: ALP accumulation (typically observed in normal articular cartilage) was lost in both the ipsilateral and the contralateral knee joints, but not in the clinically unaffected ankles of rats with AIA. In both knee joints, 123I-ALP target:background ratios and cartilage radioactivity correlated negatively with the loss of toluidine blue staining in cartilage, which documents the depletion of charged matrix molecules. Findings of histopathology confirmed mild alterations in the ipsilateral knee joint and even milder alterations in the contralateral knee joint, while the ankles were normal. Radiography and high-resolution ex vivo MRI failed to detect abnormalities in the contralateral knee joint. CONCLUSION: Loss of ALP accumulation appears to document proteoglycan depletion, even in the microscopically altered cartilage of the contralateral knee joint in AIA. These findings underscore the high sensitivity of 123I-ALP for in vivo detection of biochemical cartilage alterations in arthritis, and furthermore, question the use of the contralateral knee joint as a normal control in AIA.

[Laminin-5 in diseases of the oral cavity]. / Laminin-5 bei Erkrankungen der Mundhöhle.

The basement membrane molecule laminin forms a family of proteins. Laminin-5 was identified as key protein in the anchoring filaments of the basement membrane. The anchoring filaments connect the basement membrane to the epithelial cells and together form the epithelial adhesion complex. Disturbances in the epithelial adhesion complex result in subepithelial blistering dermatosis. Autoantibodies against laminin-5 are found in cicatricial pemphigoid. Mutations in genes of laminin-5 with loss of the protein cause epidermolysis bullosa Herlitz. It can be determined during prenatal genetic diagnostic testing. Laminin-5 supports migration of keratinocytes and forms the basis for migrating keratinocytes in oral wound healing. Positive re-epithelialization via laminin-5 has been the subject of experimental studies. Oral squamous cell carcinomas are found to have a focal loss of laminin-5 in conjunction with a loss of the cellular receptor, and increased synthesis of laminin-5 by budding tumor cells has been observed along with deposition of the protein in the stroma. As a result of these observations laminin-5 has been suggested as a route of invasion. Quantitative assessment of this phenomenon and the modulation of laminin-5-tumor cell interaction offer new and hopeful means of describing and affecting the invasive behaviour of oral squamous carcinoma.

The prevalence of orthostatic hypotension during physiotherapy treatment in patients with an acute spinal cord injury.

STUDY DESIGN: Prospective, observational. OBJECTIVES: To investigate the prevalence of orthostatic hypotension (OH), its associated signs and symptoms, and the resulting limitation to treatment during initial physiotherapy treatments involving mobilisation for patients with an acute spinal cord injury (SCI). SETTING: Spinal Injuries Units, Royal Adelaide Hospital and Hampstead Rehabilitation Centre, Adelaide, South Australia. METHODS: Fourteen of 17 consecutive patients admitted with an acute SCI completed the study. Non-invasive measurement of systolic and diastolic blood pressure (BP), heart rate and percutaneous oxygen saturation were recorded during a 10-min baseline period with the patient resting in supine, and then at 1-min intervals for the first 10 min of physiotherapy treatments that involved mobilisation (ie sitting or standing). Following cessation of the treatment and return to the supine position, further measurements were made immediately and following 5 min of rest. Visual signs and patient reported symptoms of OH and any perceived limitation to therapy were also recorded. The study period comprised the first 10 physiotherapy treatments that involved mobilisation. RESULTS: BP changes indicative of OH occurred during 73.6% of mobilisation treatments. Of these treatments, accompanying signs and symptoms of OH were noted on 58.9% of occasions and were perceived as limiting treatment on 43.2% of occasions. Patients with tetraplegia had a higher prevalence of OH and a greater fall in BP than patients with paraplegia, irrespective of whether their lesion was complete or incomplete. CONCLUSION: Blood pressure changes indicative of OH and accompanying signs and symptoms of OH are a common occurrence during the physiotherapy mobilisation of patients with an acute SCI.

Experimental studies on the stem cell concept of liver regeneration. II.

There is increasing evidence in support of the existence of a hepatic stem or progenitor cell system as well as its participation in the physiological as well as reparative regeneration of the liver and in carcinogenesis. In the present paper it will be demonstrated that under the condition of a simultaneous intoxication with allyl alcohol and tetrachlorcarbon a regenerative process occurs, which is composed of two distinct partial processes: 1. a "proliferative wave" of the persisting, non-necrotic differentiated hepatocytes of the acinus, starting at 24 h after intoxication and ending after >48 h, and 2. a proliferation of cells at the rim of the portal fields, which afterwards enter the acinus and differentiate into hepatocytes, starting at 48 h after intoxication. These results support the participation of a stem or progenitor cell system in the reparative regeneration of the liver.

Evaluation of microvessel density by computerised image analysis in human renal cell carcinoma. Correlation to pT category, nuclear grade, proliferative activity and occurrence of metastasis.

A high microvessel density is suspected to favour tumour progression and the occurrence of metastasis. To elucidate the significance of abundant vessels for the behaviour of human renal carcinomas, the microvessel density of 110 renal cell carcinomas was correlated to pT category, nuclear grade, proliferative activity, occurrence of metastasis and relapse-free survival interval. The microvessels were quantified using CD31 immunostaining of endothelial cells and computer-aided image analysis. The rules for reproducible microvessel counting, as defined by Weidner, were strictly observed. A statistically significant relationship between the microvessel density and nuclear grade, proliferative activity, occurrence of metastasis and relapse-free survival was found; only for tumour size could no such relation be seen. Perplexingly, there is a diminution of microvessel density in association with increasing nuclear grade, proliferative activity, relapse-free survival interval and frequency of metastasis. This finding is contradictory to the hypothesis that an increasing microvessel density indicates a worsening prognosis.