[Distal femur replacement in extensive defects of the distal femur in revision arthroplasty]. / Distaler Femurersatz bei ausgedehnten femoralen Defekten in der Revisionsendoprothetik.

OBJECTIVE: Use of distal femur replacement implants in advanced bone defects after multiple bone-damaging revision surgery on the knee joint. INDICATIONS: Advanced femoral bone defects (AORI IIb and III defects) in revision arthroplasty of the knee joint. CONTRAINDICATIONS: Persistent or current joint infection, general infection, defect and/or nonreconstructable insufficient extensor apparatus. SURGICAL TECHNIQUE: Standard access including existing skin scars, arthrotomy, removal of cement spacer if necessary and removal of multiple tissue samples; preparation of tibia first to define the joint line, then preparation of the femur. Determining the resection height of the remaining femur corresponding to the preoperative planning. Gradual drilling using flexible medullary drills and then preparation by femoral rasps. Two stem systems are available for coupling to the distal femur (MUTARS). First there is the standard MUTARS stem (available lengths of 90, 120 and 160 mm); if longer shafts are required, so-called revision shaft (RS) stems are necessary (stems available in 150, 200 and 250 mm). In case of extensive femoral defects extension sleeves in different lengths can be used to reconstruct the femur. After preparation the implant position and the joint line height is checked. POSTOPERATIVE MANAGEMENT: Full weight bearing, in case of existing bony defects possibly partial load of a maximum of 10 kg für 6 weeks; regular wound control; limitation of the degree of flexion only with weakened or reconstructed extensor apparatus. RESULTS: Between February 2015 and August 2018, a total of 34 distal femurs were implanted. In 19 patients, the implantation was performed after septic and aseptic loosening of a knee prosthesis. All patients had an intraoperative AORI III defect of the femur. Of the 19 patients who underwent a distal femur implantation, 7 had to be revised due to a persistent infection; 4 of these 7 patients had to be revised several times and, finally, had a conversion to a knee arthrodesis. One patient had to undergo a revision with a stem change due to a secondary aseptic loosening of the cemented stem. The mean follow-up period was 11.2 months (range 4-29 months). The follow-up included clinical examination, KSS (Knee Society Score) and X­ray analysis. A significant improvement in range of motion from 65 ± 16° to 83 ± 14° (p < 0.01) was noted. The KSS improved significantly from 69 ± 9 points preoperatively to 115 ± 15 points postoperatively. Four patients complained of persistent symptoms during exercise after 9 months; femoral shaft pain was denied by all patients. After about 11 months, an implant survival rate of 73.7% was observed in the patient collective.

Proposal for a National Blueprint Framework to Monitor Progress on Water-Related Sustainable Development Goals in Europe.

The 17 Sustainable Development Goals (SDGs) underpinned by 169 targets presents national governments with huge challenges for implementation. We developed a proposal for a National Blueprint Framework (NBF) with 24 water-related indicators, centered on SDG 6 (clean water and sanitation for all), each with a specific target. We applied the NBF to 28 EU Member States (EU-28) and conclude that: (1) The current SDG 6 indicators are useful for monitoring progress toward water-related targets but their usefulness can be improved by focusing more on their practical implementation. (2) The extension of SDG 6 with complementary indicators (e.g. for the circular economy of water) and quantitative policy targets is urgently needed. This will benefit the communication process and progress at the science-policy interface. (3) SDG indicators can be improved in a SMART (specific, measurable, achievable, relevant, and time-bound) manner and by setting clear policy targets for each indicator, allowing for measuring distance-to-targets. This allows country-to-country comparison and learning, and accelerates the SDG implementation process. (4) We propose 24 water-related indicators centered on SDG 6, with complementary indicators including quantitative policy targets. The approach is doable, easily scalable, and flexibly deployable by collecting information for the EU-28. (5) Main gaps in the EU-28 are observed for water quality, wastewater treatment, nutrient, and energy recovery, as well as climate adaptation to extreme weather events (heat, droughts, and floods). (6) The framework was less successful for non-OECD countries due to lack of data and EU-centric targets for each indicator. This needs further research.

Enhancing domestic water conservation behaviour: A review of empirical studies on influencing tactics.

The world faces imminent drought-related challenges that, from a tap-water supply perspective, require increasingly expensive infrastructure enhancement and energy expansion to maintain sufficient service levels. This paper argues that enhancing domestic water conservation provides a promising alternative or necessary addition to reduce costs and to stimulate pro-environmental behaviour. Although the number of field experiments on how people's behaviour can be changed with respect to their daily water consumption is growing, to date, most studies in this field have focussed either on explanatory socio-economic factors (e.g. water pricing, income, or family composition) or behavioural intentions and personal characteristics related to behavioural change. Accordingly, there is limited empirically validated knowledge about the use and effectiveness of different influencing tactics to change behaviour. This paper provides a review of the empirically oriented literature in this field and aims to provide an up-to-date assessment that identifies eight different Behavioural Influencing Tactics (BITs) that target long-term water conservation behaviour within households. Our analysis is structured around three information processing routes: the reflective route, the semi-reflective route, and the automatic route. We conclude that the current body of literature is promising and provides a useful body of evidence on the range and effectiveness of individual water conservation mechanisms, but that needs further development to deepen our understanding of how to effectively prolong and reinforce newly formed water conservation routines.

A nondimensional normalization scheme for oxygen utilization data.

The total oxygen required for gait (gross utilization) is a widely used indicator of locomotor efficiency. The standard scheme of mass normalization (dividing gross utilization by mass) is intended to eliminate confounding effects that arise from variations in age and size. Despite its prevalence, mass normalization has been shown to be inadequate, as the normalized quantity retains a marked dependence on clinically relevant factors. The current study proposes a new scheme for normalizing oxygen utilization data. The new scheme, called net-nondimensional normalization, is based on the use of net oxygen utilization (gross-rest) and nondimensional gait variables. Measures of statistical significance are employed to demonstrate that net nondimensional normalization is superior to mass normalization. Net nondimensional oxygen utilization is shown to be largely independent of the relevant physiological and anatomical factors, and is therefore well suited for studies where an independent measure of gait efficiency is needed.

Measurement accuracy in congenital scoliosis.

BACKGROUND: The accuracy of measurement of curves in idiopathic scoliosis has been extensively studied; however, we know of only one article in the literature concerning the accuracy of measurement of curves in congenital scoliosis. That article stated that intraobserver variability was +/- 9.6 degrees and interobserver variability was +/- 11.8 degrees. METHODS: Sixty-nine curves in fifty patients with congenital scoliosis were measured on two separate occasions by seven different observers with varying experience in curve measurement. RESULTS: Mean intraobserver variance ranged from 1.9 degrees to 5.0 degrees, with an average of 2.8 degrees (95% confidence limit, +/- 3 degrees) for the seven observers. The interobserver variance was 3.35 degrees (95% confidence limit, 7.86 degrees). CONCLUSIONS: It is possible to measure curves in congenital scoliosis with much greater accuracy than previously reported. In the clinical situation in which a skilled observer can measure two radiographs at the same time, an accuracy of +/- 3 degrees can be expected 95% of the time.

Determination of "normal" thoracic kyphosis: a roentgenographic study of 121 "normal" children.

The purpose of this prospective study was to determine the range of "normalcy" in the radiologic measurement of thoracic kyphosis in children by using a standardized position and full-length radiograph in 121 normal children. Using +/- two standard deviations from the mean as the definition of "normal," a range of 20 degrees - 50 degrees was determined. There was no difference between the various age subgroups or between genders.

Use of ML dipstick as a tool to classify leprosy patients.

Leprosy control services face the problem of leprosy patients being misclassified by the lack of or the poor quality of skinsmear examination services. Misclassification increases the risk of relapse due to insufficient treatment if a multibacillary (MB) patient is classified as paucibacillary (PB), thereby also prolonging the time that the patient is infectious. The World Health Organization (WHO) recommends at present an alternative classification based on the number of skin lesions. Its reliability, however, has been questioned. Our investigation sought to determine the usefulness of the ML Dipstick, a simple field assay to detect IgM antibodies to phenolic glycolipid-I of Mycobacterium leprae, for the classification of leprosy patients in addition to lesion count. In this study, 264 leprosy patients were investigated. Of 130 patients with a positive bacterial index (BI), 19 (14.6%) had less than 6 lesions and would have been classified as PB. Out of 134 patients with a negative BI, 26 (19.4%) had 6 or more lesions and would have been classified as MB patients if the lesion counting system would apply. Thus, the classification based on the number of lesions only was found to be 85% sensitive and 81% specific (using the BI as the gold standard) at detecting MB cases among the studied population. Sensitivity would have increased if patients would have been classified according to a combination of the number of lesions and the dipstick result. In that case patients are classified as MB when they are either dipstick positive (N = 16), have more than 6 lesions (N = 43), or both (N = 94). Patients negative for both dipstick and number of lesions would have been classified as PB (N = 111). The classification based on the number of lesions alone left 19 BI-positive cases classified as PB, while the combination method of the ML Dipstick and number of lesions left only 8 BI-positive cases classified as PB (5 borderline, 2 borderline lepromatous and 1 tuberculoid), thus preventing undertreatment. The combination method of the ML Dipstick and lesion counting was found to be 94% sensitive and 77% specific, which is an improvement of 9% (chi-squared test, p = 0.025) in sensitivity compared to lesion counting only. The results of this study indicate that testing all patients initially classified by lesion counting as PB (48% in our study population) with the dipstick can significantly contribute to improved classification of leprosy patients for treatment purposes.

Spinal instrumentation without fusion for progressive scoliosis in young children.

Between 1973 and 1993, a heterogeneous group of 67 children with progressive scoliosis entered a program of incremental-distraction spinal instrumentation without fusion supplemented by full-time external orthotic support. Over the course of treatment, curve magnitude improved from an average of 67 degrees at initial instrumentation to 47 degrees at definitive fusion. For all patients, curve response tended to decline with consecutive procedures. The measured growth of the instrumented but unfused spinal segments averaged 3.1 cm over a mean treatment period of 3.1 years. The results of our study suggest that spinal instrumentation without fusion can control progressive scoliosis in a majority of children while allowing normalized growth of instrumented spinal segments. The mean duration of treatment and ultimate gain in spinal length are constrained by progressive structural changes that alter curve response to incremental distraction. Despite these limitations, spinal instrumentation without fusion may provide a reasonable management alternative when individualized among these difficult patients.

Three common causes of childhood hip pain.

Disorders of the hip that result in pain during childhood are not random and chaotic events. The work of numerous investigators demonstrates that each condition has distinguishing characteristics. These characteristics are found in the manner of presentation, the physical examination, and the diagnostic study. Familiarity, with these conditions, attention to the details of the patients' history, and a careful eye for the details of physical examination allow skillful physicians to devise a plan of investigation that results in a successful diagnosis.

Independence of metastatic ability and extravasation: metastatic ras-transformed and control fibroblasts extravasate equally well.

Escape of cancer cells from the circulation (extravasation) is thought to be a major rate-limiting step in metastasis, with few cells being able to extravasate. Furthermore, highly metastatic cells are believed to extravasate more readily than poorly metastatic cells. We assessed in vivo the extravasation ability of highly metastatic ras-transformed NIH 3T3 cells (PAP2) versus control nontumorigenic nontransformed NIH 3T3 cells and primary mouse embryo fibroblasts. Fluorescently labeled cells were injected intravenously into chicken embryo chorioallantoic membrane and analyzed by intravital videomicroscopy. The chorioallantoic membrane is an appropriate model for studying extravasation, since, at the embryonic stage used, the microvasculature exhibits a continuous basement membrane and adult permeability properties. The kinetics of extravasation were assessed by determining whether individual cells (n = 1481) were intravascular, extravascular, or in the process of extravasation, at 3, 6, and 24 h after injection. Contrary to expectations, our results showed that all three cell types extravasated with the same kinetics. By 24 h after injection > 89% of observed cells had completed extravasation from the capillary plexus. After extravasation, individual fibroblasts of all cell types demonstrated preferential migration within the mesenchymal layer toward arterioles, not to venules or lymphatics. Thus in this model and for these cells, extravasation is independent of metastatic ability. This suggests that the ability to extravasate in vivo is not necessarily predictive of subsequent metastasis formation, and that postextravasation events may be key determinants in metastasis.

Steps in tumor metastasis: new concepts from intravital videomicroscopy.

Metastases are responsible for the majority of failures in cancer treatment. Clarifying steps in metastasis and their molecular mechanisms will be important for the development of anti-metastasis therapeutic strategies. Considerable progress has been made in identifying molecules involved in metastasis. However, because of the nature of assays that have been available, conclusions about steps in metastasis and their molecular bases have been drawn primarily from inference. In order to complete the picture of how metastases form, a technique is needed to directly watch the process in vivo as it occurs over time. We have developed an intravital videomicroscopy (IVVM) procedure to make such observations possible. Results from IVVM are providing us with new conceptual understanding of the metastatic process, as well as the nature and timing of the contributions of molecules implicated in metastasis (e.g. adhesion molecules and proteinases). Our findings suggest that early steps in metastasis, including hemodynamic destruction and extravasation, may contribute less to metastatic inefficiency than previously believed. Instead, our results suggest that the control of post-extravasation growth of individual cancer cells is a significant contributor to metastatic inefficiency. Thus, this stage may be an appropriate target for design of novel strategies to prevent metastases.

Effects of the disintegrin eristostatin on individual steps of hematogenous metastasis.

Adhesion molecules, including integrins, are important for interactions of cancer cells with vessel walls, a step leading to cancer metastasis. Disintegrins block the action of integrins by binding to them. We tested the hypothesis that the disintegrin eristostatin would block metastasis by interfering with cancer cell adhesion to vessel walls, thus preventing extravasation. Experimental metastasis assays, in which B16F1 melanoma cells (controls vs eristostatin-treated, 25 micrograms/ml) were injected via mesenteric veins of anesthetized C57BL/6 mice, showed that eristostatin reduced (P < 0.05) the mean number of liver metastases from 14.4 to 0.6 at 11 days postinjection (p.i.). We examined three different steps in metastasis at which eristostatin could have exerted its effect, namely, cell arrest, extravasation, and migration. Control and eristostatin-treated B16F1 cells were fluorescently labeled and examined by videomicroscopy in liver microcirculation in vivo at various times up to 14 days p.i. Measurements of vessel size in which cell arrest occurred and length/width ratio of arrested cells showed only small differences between control and eristostatin-treated cells. Eristostatin treatment did not prevent extravasation, and the timing and process of extravasation were similar for both treated and control cells; by 3-4 days p.i. more than 90% of the cells had extravasated or were in the process. Eristostatin also did not affect the ability of extravasated cells to migrate through the extracellular matrix to the subcapsular region where tumors later form. Therefore, we conclude that eristostatin exerted its primary effect by regulating the number of individual cancer cells that grow after extravasation.

Fate of melanoma cells entering the microcirculation: over 80% survive and extravasate.

Metastasis is an inefficient process; only a few cancer cells are able to form tumors after being released into the circulation. We studied the fate of cancer cells after injection into the circulation, quantifying their survival and ability to extravasate by 1 day later. B16F10 cells, parental or transfectants overexpressing tissue inhibitor of metalloproteinases 1, were injected i.v. into chorioallantoic membrane of chick embryos and analyzed by intravital videomicroscopy. Cell survival was quantified in two ways: (a) 15-microns microspheres were injected with cancer cells, and proportions of viable cells to microspheres were compared before and after injection; and (b) individual cancer cells were monitored continuously for 0.5-8-h intervals covering the first 24 h. Both methods showed virtually no destruction of cells. Greater than 80% of injected cells survived and extravasated by 24 h, indicating that growth after extravasation is a key stage of metastatic control.

Mammary carcinoma cell lines of high and low metastatic potential differ not in extravasation but in subsequent migration and growth.

We examined the extravasation and subsequent migration and growth of murine mammary tumor cell lines (D2A1 and D2.OR) which differ in their metastatic ability in lung and liver, invasiveness in vitro and expression of the cysteine proteinase cathepsin L. In light of the differences in invasiveness and cathepsin L expression, we hypothesized that during hematogenous metastasis the two cell lines would differ primarily in their ability to extravasate. We used in vivo videomicroscopy of mouse liver and chick embryo chorioallantoic membrane to examine the process and timing of extravasation and subsequent steps in metastasis for these cell lines. In contrast to our expectations, no differences were found between the cell lines in either the timing or mechanism of extravasation, at least 95% of cells having extravasated by 3 days after injection. However, after extravasation, the more metastatic and invasive D2A1 cells showed a greater ability to migrate to sites which favor tumor growth and to replicate to form micrometastases. These studies point to post-extravasation events (migration and growth) as being critical in metastasis formation.

Overexpression of metalloproteinase inhibitor in B16F10 cells does not affect extravasation but reduces tumor growth.

It is widely accepted that a major role of matrix metalloproteinases in the metastatic process is degradation of basement membrane during cancer cell invasion. We tested the hypothesis that the reduction in metastatic potential which has been demonstrated for B16F10 melanoma cells genetically engineered to overexpress tissue inhibitor of metalloproteinase-1 (TIMP-1) is caused by a decrease in their ability to extravasate. Using intravital videomicroscopy of chick embryo chorioallantoic membrane, we studied extravasation of B16F10 cells and B16F10 cells transfected to overexpress TIMP-1. More than 800 cells in 36 chick embryos were analyzed for each cell line during 72 h postinjection. TIMP-1 upregulation had no effect on the time course of extravasation, virtually all cells from both cell lines having extravasated by 36 h. We also studied the morphology of micrometastases at days 3 and 7. Lack of contact between cancer cells within micrometastases at day 3 and reduction in size and number of tumors at day 7 were observed for TIMP-1 overexpressor cells compared to B16F10. Our findings illustrate that the imbalance between TIMP and metalloproteinases created by overexpression of TIMP-1 in B16F10 cells reduces their metastatic ability in vivo by affecting tumor growth postextravasation.

Syringomyelia and scoliosis: a review of twenty-five pediatric patients.

A retrospective review of 25 patients with scoliosis secondary to syringomyelia was conducted. All patients had large syrinxes, but only 10 patients had abnormal neurologic findings, suggesting that subtle neurologic findings in patients with scoliosis should not be underestimated and supporting liberal use of magnetic resonance imaging (MRI). The results of three approaches to the care of these patients were reviewed: passive observation, bracing, and spinal fusion. Curves progressed > or = 5 degrees in patients aged < 10 years who were observed, but in children aged > 10 years, curves progressed > or = 10 degrees. Curves responded well to bracing, but correction was not maintained out of brace for patients with progressive and/or severe curves. Good corrective was achieved safely during operation.

Early interactions of cancer cells with the microvasculature in mouse liver and muscle during hematogenous metastasis: videomicroscopic analysis.

Biomechanical interactions of cancer cells with the microvasculature were studied using high resolution intravital videomicroscopy. We compared initial arrest of murine B16F10 melanoma and D2A1 mammary carcinoma cells fluorescently labelled with calcein-AM, in low pressure (liver) vs high pressure (cremaster muscle) microvascular beds. Cells were arrested due to size restriction at the inflow side of the microcirculation, penetrating further and becoming more deformed in muscle than liver [median length to width ratios of 3.3 vs 1.3 for D2A1 cells, and 2.5 vs 1.2 for B16F10, at 1 min post-injection (p.i.)]. During the next 2 h many cells became stretched, giving maximum length to width ratios of 68 vs 22.1 (D2A1) and 28 vs 5.6 (B16F10) in muscle vs liver. Ethidium bromide exclusion demonstrated that over 97% of the cells maintained membrane integrity for > 2 h p.i. (In contrast, when an acridine orange labelling procedure was used, membrane disruption of B16F10 cells occurred within 15 min p.i.) Our experiments do not indicate the ultimate fate of the cancer cells, but if cell lysis occurs it must be on a time scale of hours rather than minutes. We report a process of 'clasmatosis' in cancer cells arrested in the microcirculation: large membrane-enclosed fragments (> 3 microns in diameter) became 'pinched off' from arrested cells, in both liver and muscle, often within minutes or even seconds of arrest. The significance of this process is not yet understood. In this study intravital videomicroscopy has thus provided a valuable clarification of the interactions of cancer cells with vessel walls during metastasis.

[Treatment of deformities of the locomotor system in hemiplegia]. / Die Behandlung der Deformitäten am Bewegungsapparat bei Hemiplegie.

In spastic hemiplegia mainly one side of the body is affected. In both the upper and the lower extremity the distal parts (hand and foot) are more severely involved than the proximal region. In cases of minor involvement the goal of treatment in the upper extremity is to achieve functional improvement by means of splinting and surgery. In cases of severe alterations cosmetic improvement without much functional gain is all that can be expected. Gait analysis has demonstrated that there are four basic patterns that can be related to the severity of involvement. In type I muscle imbalance exists without a contracture. In type II there is contracture of the muscles of the posterior compartment of the calf. In type III, in addition to the changes around the ankle joint, contractures around the knee are present, and in type IV also hip problems. Functional improvement can be achieved by means of splinting and surgery in all types. Basic principles of treatment have developed as a result of the application of gait analysis and dynamic electromyography. Specific examples of such treatment principles have recently been presented by Gage.

Luque-Galveston procedure for correction and stabilization of neuromuscular scoliosis and pelvic obliquity: a review of 68 patients.

Sixty-eight patients with neuromuscular spine deformity were treated by posterior spine fusion with Luque-Galveston instrumentation between 1982 and 1986. The minimum follow-up was 4 years. Diagnoses included cerebral palsy in 34 patients and other neuromuscular diseases in another 34 patients. The average age was 14 years. Twenty patients also had anterior spine fusion without instrumentation. Preoperatively the average scoliosis was 73 degrees and this was corrected to 33 degrees at final follow-up. The subgroup having anterior discectomy and fusion had a more severe scoliosis and pelvic obliquity, but the percent of correction was similar to that of the group with posterior reconstruction only. Twenty-four patients who had an associated significant sagittal plane deformity were corrected to a physiologic curvature. A postoperative thoracolumbosacral orthosis was used in 27 patients, and a molded seating orthosis was used in 18. Although the rate of complications was high (62%), most of them were minor. Instrumentation problems occurred in 14 patients (21%), only 4 of them having broken rods. There were no broken wires. Pseudarthrosis occurred in seven patients (10%). Three patients had minor neurologic deficits, all transient. The "windshield-wiper" sign was defined as any radiolucency of 2 mm or greater. Twenty-six patients had this sign at follow-up, and this group had a higher percentage of complications, but the existence of this sign did not necessarily indicate a problem.

Management of neuromuscular spinal deformities with Luque segmental instrumentation.

Forty-six patients who had a neuromuscular spinal deformity were treated with arthrodesis and Luque segmental spinal instrumentation and were followed for an average of three years. Twenty-two patients had cerebral palsy and twenty-four had another neuromuscular disease. In thirty-nine patients, the arthrodesis was extended to the sacrum. Eleven patients who had severe scoliosis as well as pelvic obliquity and decompensation of the torso had a combined anterior and posterior arthrodesis; the other thirty-five patients had a one-stage posterior procedure. Preoperatively, the average scoliosis was 74 degrees; this was corrected to 39 degrees at follow-up. Final corrections were similar for scoliosis and were better for pelvic obliquity and decompensation of the torso in patients who had combined anterior and posterior arthrodesis. The results for scoliosis and pelvic obliquity in patients who had a spastic deformity were similar to the results in patients who had a flaccid deformity. Correction of decompensation of the torso was better in patients who had a spastic deformity. Postoperatively, a brace was used in half of the patients in each group; this did not appear to affect the amount of correction in either group, although the result may have been influenced by the selection process. The rate of complications was 48 per cent. Pseudarthrosis occurred in three patients (6.5 per cent). There were no major neurological deficits related to the correction or to the use of sublaminar wires. Three patients died, one in the immediate postoperative period and the other two at eighteen months and four years after the original procedure, due to causes unrelated to the operation.