Prediction of survival after surgery due to skeletal metastases in the extremities.

AIMS: The purpose of this study was to develop a prognostic model for predicting survival of patients undergoing surgery owing to metastatic bone disease (MBD) in the appendicular skeleton. METHODS: We included a historical cohort of 130 consecutive patients (mean age 64 years, 30 to 85; 76 females/54 males) who underwent joint arthroplasty surgery (140 procedures) owing to MBD in the appendicular skeleton during the period between January 2003 and December 2008. Primary cancer, pre-operative haemoglobin, fracture versus impending fracture, Karnofsky score, visceral metastases, multiple bony metastases and American Society of Anaesthesiologist's score were included into a series of logistic regression models. The outcome was the survival status at three, six and 12 months respectively. Results were internally validated based on 1000 cross-validations and reported as time-dependent area under the receiver-operating characteristic curves (AUC) for predictions of outcome. RESULTS: The predictive scores obtained showed AUC values of 79.1% (95% confidence intervals (CI) 65.6 to 89.6), 80.9% (95% CI 70.3 to 90.84) and 85.1% (95% CI 73.5 to 93.9) at three, six and 12 months. DISCUSSION: In conclusion, we have presented and internally validated a model for predicting survival after surgery owing to MBD in the appendicular skeleton. The model is the first, to our knowledge, built solely on material from patients who only had surgery in the appendicular skeleton. TAKE HOME MESSAGE: Applying this prognostic model will help determine whether the patients' anticipated survival makes it reasonable to subject them to extensive reconstructive surgery for which there may be an extended period of rehabilitation. Cite this article: Bone Joint J 2016;98-B:271-7.

Peak and ceiling effects in final-product analysis of mastoidectomy performance.

BACKGROUND: Virtual reality surgical simulation of mastoidectomy is a promising training tool for novices. Final-product analysis for assessing novice mastoidectomy performance could be limited by a peak or ceiling effect. These may be countered by simulator-integrated tutoring. METHODS: Twenty-two participants completed a single session of self-directed practice of the mastoidectomy procedure in a virtual reality simulator. Participants were randomised for additional simulator-integrated tutoring. Performances were assessed at 10-minute intervals using final-product analysis. RESULTS: In all, 45.5 per cent of participants peaked before the 60-minute time limit. None of the participants achieved the maximum score, suggesting a ceiling effect. The tutored group performed better than the non-tutored group but tutoring did not eliminate the peak or ceiling effects. CONCLUSION: Timing and adequate instruction is important when using final-product analysis to assess novice mastoidectomy performance. Improved real-time feedback and tutoring could address the limitations of final product based assessment.

The effect of selection for high-level vector expression on the genetic and functional stability of a single transcript vector derived from a low-leukemogenic murine retrovirus.

Single-gene murine leukemia virus-based retroviral vectors carrying the G418-resistance gene (neo) under transcriptional control of the long terminal repeat were used to study the effect of selection on long-term vector expression in a murine lymphoid cell line, L691. We used two isogenic vectors carrying either a strong or a weak transcriptional enhancer from low-leukemogenic Akv and high-leukemogenic SL3-3 murine leukemia virus, respectively. Effects of G418 selection were studied at the level of vector-transduced cell populations and at the level of single-vector-transduced cell clones obtained without selection for vector expression. Selection for vector expression prior to isolation of cell clones changed the range of vector expression for the two populations of cell clones. Cell clones harboring the Akv enhancer, isolated without selection and then subjected to prolonged growth under selective conditions, exhibited no mutations in the enhancer region or major vector rearrangements although showing increased vector expression in some cases. Our results are discussed in terms of retrovirus-mediated gene transfer strategies employing selection for expression of a selective marker in single-gene or bicistronic vectors with a low- or nonleukemogenic virus-derived backbone.

Measurement of hygromycin B phosphotransferase activity in crude mammalian cell extracts by a simple dot-blot assay.

Hygromycin B (Hy) resistance, encoded by the prokaryotic gene hph, is commonly used as a dominant selectable marker for gene transfer experiments in mammalian cells. We describe a simple, quantitative dot-blot assay for measuring the activity in crude mammalian cell extracts of Hy phosphotransferase, the product of the hph gene. The assay shows no cross interference with substrates for neomycin phosphotransferase II, the product of the commonly used marker gene neo; hph and neo may thus be useful as a set of two non-interfering selectable marker and reporter genes for gene transfer experiments in mammalian cells.

Volume-referent bone turnover estimated from the interlabel area fraction after sequential labeling.

In the compact bony otic capsule remodeling is low, and bone remodeling units are distributed centrifugally in relation to inner ear tissues and spaces. Fluorochrome-labeled bone remodeling units are scarce, abortive, and tortuous with no uniform direction of movement. This study presents a method for the estimation of volume-referent bone turnover based on measurements of the fractional area between labels after sequential labeling with osteofluorochromes. The applicability of this method is tested against a classical quantification method in undecalcified cortical specimens from the canine humerus, where both methods can be used. The estimate of bone turnover derived from the new sequential labeling in eight dogs is 7.4% (SEM 2.1%) per year and the classic estimate derived from calculations of the formative osteonal area and the formative period yields 6.9% (SEM 2.1%) per year. Agreement is sufficient to justify future measurements of absolute bone turnover in sequentially labeled perilabyrinthine bone.

Remodeling patterns in the bony otic capsule of the dog.

Quantum-type bone remodeling was studied in undecalcified temporal bones and long bone specimens from adult mongrel dogs by means of combined microradiography, osteofluorochrome labeling, and osteoid staining. The overall turnover rate of capsular bone was estimated to be low compared to that of extracapsular compact bone. Evolving secondary osteons were distributed centrifugally relative to the perilymphatic space. Moreover, a zone of bone tissue enclosing perilymphatic spaces was found completely devoid of evolving secondary osteons. Throughout the otic capsule, segmentary perivascular foci of resorption and formation were present. These findings indicate that remodeling of capsular bone is subject to sustained local inhibition. The significance of this conclusion is considered with special reference to otosclerosis.

Demonstration of intravital microfissures in undecalcified plastic-embedded temporal bones with the prestaining technique.

Microfissures in the human otic capsule have been observed since the start of the century, but it was Otto Mayer, in 1930, who first realized that some of them were of intravital origin and not just processing artifacts. Since then, a small number of publications, based on decalcified temporal bones, have mostly confirmed his findings. With the introduction by Frost in the late 1950s of the undecalcified bone technique and the bulk staining technique for peripheral bones, a method was developed and refined for identifying even very small intravital microfissures (microdamage). Bulk staining of undecalcified otic capsules has not yet been used to verify the findings from the previous decalcified specimens. The present report presents our experience with the pertinent techniques, and suggests modifications and shortcuts pertinent to temporal bone research. Both large and tiny microfissures of intravital genesis are demonstrable within bulk-stained undecalcified human otic capsules. The importance of microfissures in the petrous bone in the causation of otosclerosis and perilymphatic leakage has long been discussed, and the present techniques may advance our understanding of these pathological conditions

Estimation of volume referent bone turnover in the otic capsule after sequential point labeling.

Using fluorochrome labeling and a newly validated method for bone turnover estimation, we determined absolute values for canine perilabyrinthine bone remodeling. The overall capsular bone turnover was found to be 2.1% per year, compared to 13.9% per year for the neighboring cranial bones and 7.4% per year for the humerus compacta. This gross 2.1% per year conceals a vast range, from 0.13% per year for the innermost perilymphatic zone, through a centrifugal increment toward 8% to 10% per year in the periphery. The underlying individual bone remodeling units exhibit a similar centrifugal pattern in numerical density and size. These findings indicate an inhibition of remodeling, seemingly emanating from the perilymphatic spaces, and affecting both the activation of osteoclasts and the extent of resorption by the osteoclasts. These values satisfactorily explain the preservation of such fetal remnants as the globuli ossei, the interglobular spaces, and the skein bone. In humans, local ineffective inhibition of bone resorption may play a role in the initiation of otosclerosis.

Fibrodysplasia ossificans progressiva and hearing loss.

A case of Fibrodysplasia ossificans progressiva is presented, in which conductive hearing loss was one of the typical clinical features. The implications of hearing loss in this group of patients are discussed.

Distribution of bone remodeling units in the otic capsule of the rabbit. A semiquantitative morphometric study.

Distribution of bone remodeling units (BRU) in relation to the perilymphatic space was studied in undecalcified temporal bones from adult rabbits labeled in vivo with bone-seeking fluorochromes. Based on recordings of focal bone formation, relative densities of BRUs inside concentric tissue zones around the inner ear spaces were estimated. Zonal densities of BRUs were found to decline towards the perilymphatic space, lending further support to the existence of a local inner ear mechanism in control of capsular bone tissue dynamics. The possible nature of this mechanism is considered briefly with special reference to inner ear electromechanic activity.

Bone modeling in the otic capsule of the rat.

Bone modeling determines postuterine gross bone architecture. During growth the shape and proportion of all bones are continuously adapted to function by surface resorption and surface formation. This process is responsible for exchange of most primary endochondral type bone with lamellar endosteal or periosteal bone. By a combination of microradiography, tetracycline fluorescence and osteoid staining of undecalcified material bone modeling in the otic capsule of the rat was studied and compared to well-known modeling patterns in rat long bones. Perilymphatic spaces were found to be enclosed in a layer of primary bone resistant to resorption associated with surface modeling. It is proposed, that this drift barrier is maintained by a control mechanism present inside the perilymphatic space.

Quantum type bone remodeling in the otic capsule of the pig.

Normal quantum type bone remodeling was studied in temporal bones of young domestic pigs by means of combined microradiography, osteofluorochrome labelling and osteoid staining. Evolving secondary osteons were morphologically normal although much less in the otic capsule than in the surrounding compacta of the temporal bones or in long bones. Moreover, remodeling was totally absent in bone tissue immediately adjacent to perilymphatic spaces suggesting the presence of a local mechanism controlling resorption and perhaps formation in the bony otic capsule.

Bone repair in the otic capsule of the rabbit.

The repair of 1 mm drill hole lesions in rabbit long bones and otic capsules was studied in undecalcified sections. Following surgery, bone formation was monitored during 12 weeks by intravital sequential time labeling with bone-seeking fluorochromes. In diaphyseal bone, initial repair by trabecular woven bone was accompanied by a transient remodeling response in primary repair bone and the surrounding compacta. In comparison, capsular defects showed a slightly deficient initial repair by woven bone which, once formed, persisted unchanged with no subsequent osteonal remodeling. In the surrounding capsule, the remodeling response was subtle and its duration much shorter. Moreover, the centrifugal distribution of bone remodeling units around inner ear spaces was preserved, suggesting that capsular repair is affected by the same morphogenetic field that controls perilabyrinthine growth, modeling and remodeling. The significance of these findings is briefly discussed in relation to otosclerosis and cochlear implant strategies.

Temporal bone dynamics, the hard way. Formation, growth, modeling, repair and quantum type bone remodeling in the otic capsule.

This review presents studies in which temporal bone dynamics were monitored in undecalcified human and animal materials by combined microradiography and osteofluorochromic time labeling. The results are interpreted in accordance with modern concepts of spatial and temporal organization of bone behavior in an attempt to contribute to a new basis for understanding the structure and function of the bony otic capsule. In postcartilaginous development, perilabyrinthine bone formed a separate functional unit in which growth and modeling were absent. Consequently, all drift movements bypassed the bone present inside a narrow perilabyrinthine zone, which in effect maintained a so-called drift barrier enclosing the entire inner ear. In baseline bone remodeling and repair-associated remodeling transients, secondary osteons were distributed centrifugally with respect to inner ear spaces, and the average osteonal size decreased towards the inner ear, suggesting a progressive inhibition of bone resorption towards inner ear spaces. No histological capsular component proved resistant to bone resorption during modeling and remodeling. Instead the dynamic behaviour of any moiety of capsular bone appeared to depend on its spatial relation to the membranous labyrinth rather than on histological characteristics. This spatial organization of perilabyrinthine bone development and turnover is responsible for the unique histology of capsular bone and may explain the accumulation of fatigue micro-cracks which can be found in human perila byrinthine bone. These findings suggests the role of inner ear tissues as a functional matrix in control of capsular bone dynamics even beyond fetal life.

Primary physicians and the elderly hearing-impaired. Actions and attitudes.

This study was undertaken in the Valby health district in Copenhagen in order to evaluate the activities and attitudes of GPs concerning hearing problems in their elderly patients. Among 55 GPs offering health services to the 2915 residents > or = 80 years of age in the district, 76% (n = 42) responded to a structured questionnaire or personal interview, evaluating their line of action concerning hearing problems, and their knowledge and attitudes towards hearing aids (HAs). Among the responding GPs, 7% always seek information on the hearing ability of their elderly patients at the defined age, whereas 14% never focus on the hearing; 45% of the GPs always refer to an ENT specialist when hearing problems are present, which causes further delay in the rehabilitation process and increases costs within the primary health care sector. GPs' attitudes to HAs seem to be changing in a positive way, 91% of them revealing a positive attitude to HAs, and 86% indicating that a HA is capable of ameliorating a hearing problem in the elderly. Irrespective of this positive attitude, the knowledge of types of HAs among GPs seems limited. The study cannot support the idea of making HAs prescribable by GPs unless they are first offered intensive courses on audiology.

Recognition of basic fuchsin prestained microfissures of intravital origin with fluorescence microscopy: validation of a shortcut.

For 70 years it has been suspected that not all microfissures in histological bone sections are artifacts, but that some are provoked in vivo through repetitive stress. The development of undecalcified bone techniques and of the bulk staining technique has established a method for demonstrating the existence of intravital cracks and enhanced the discrimination towards artifactual microfissures in the load-bearing skeleton. Recently the presence of intravital microfissures has also been ascertained in temporal bones by these techniques. Due to the fluorescent properties of basic fuchsin it is possible to use epifluorescence microscopy for analysis of microfissures after bulk staining with basic fuchsin. This provides a more steady microscopic background and a sharper delineation of surface level structures since no projection from lower levels interfere. Artifactual cracks, which in transmitted light microscopy may look like darkly stained intravital microfissures due to refraction phenomena, become invisible or colorless. Epifluorescence microscopy enhances the detection of both smaller and larger prestained intravital microfissures, and leaves only a minor part of the cracks without certain categorization. The epifluorescence mode of analysis has the further advantage of being independent of slice thickness, making feasible whole-specimen analysis by serial stepwise grinding. The present study shows that the number and the length of microfissures in the human otic capsule, counted and measured under the epifluorescence microscope, equals numerically the findings in light microscopy, enabling the routine use of this mode of analysis. This may prove to be of particular value in the research into the etiology and pathogenesis of otosclerosis as well as perilymphatic fistulae.

Drift barriers in the postcartilaginous development of the mammalian otic capsule.

Postcartilaginous development of the otic capsule was studied in undecalcified histological material from rabbits following sequential fluorochromic time labeling of mineralizing tissues, using combined microradiography, fluorescence microscopy and osteoid staining. Early fetal bone formation was monitored by labelling of the experimental animals in utero. In contrast to the normal pattern of drift movements displayed by long bones and extracapsular cranial bone, capsular bone inside a zone immediately surrounding the perilymphatic space developed as a separate functional unit in which growth and modeling was absent. Bone tissue behavior appeared to depend on its spatial relation to the membranous labyrinth rather than histological characteristics. These findings suggest the role of inner ear tissues as a functional matrix in control of capsular bone dynamics beyond fetal life.

Predilection of otosclerotic foci related to the bone turnover in the otic capsule.

Using multiple fluorochrome tagging of eight mongrel dogs and a newly established methodology of measuring bone turnover (BTO) in the otic capsule, it has previously been demonstrated that BTO in the canine otic capsule is highly reduced close to the perilymphatic spaces (PLS) compared to the normal level of BTO in the periphery. Reanalysis of these data shows that this inhibition of BTO is far more pronounced around the cochlea and vestibule than around the semicircular canals. Similar tendencies are seen for the numerical density and mean label area of the bone remodelling units. With increasing distance to the PLS, these patterns are weakened, but still recognizable. In otosclerosis, foci of abnormal bone deposition are particularly frequent around the oval and round windows and in the cochlear capsule, i.e. where inhibition of bone remodelling is most prominent. A surpassing (or failure) of this pronounced inhibition must precede the tumultuous but delimited osteogenesis of otosclerosis. Otosclerosis may be a deviation of the normal BTO process in an osteometabolically abnormal site, perhaps initiated as an osteogenetic response to abnormal stress exposure.

Hearing in the elderly > or = 80 years of age. Prevalence of problems and sensitivity.

This article is part of an epidemiological study on hearing in an urban population > or = 80 years of age, and concentrates on the prevalence of hearing problems and hearing sensitivity as a function of age and gender. Prior to the study, 2915 residents aged 80+ from the Valby area in Copenhagen were selected for investigation and subdivided into two groups. The first group, comprising n = 859 subjects previously provided with HA, and the second group, resulting from an invitation mailed to n = 565 subjects, were matched according to the age and gender distribution of the population, i.e. 24% males and 76% females. Among these, only 41% at a median age of 84 years, range 80-96, accepted the invitation, being significantly younger than the non-attenders. The estimated prevalence of self, reported hearing problems ranged between 33 and 66%, increasing with increasing age. Significant differences were found in the hearing sensitivity as a function of gender, i.e. the hearing in the low-frequency area < 1 kHz is better, whereas the hearing sensitivity at > 2 kHz is significantly worse in males compared with females. The speech recognition score (SRS) was significantly higher in females compared with males, and a comparison between ears supports the finding that the right ear speech recognition score is better than the left. The study demonstrates the difficulties in obtaining reliable epidemiological data on the hearing in the elderly > or = 80 years, which represents an obstacle for the planning of appropriate hearing health services directed towards this age group, and collaborative studies are suggested in order to accumulate more knowledge.

Hearing instruments and health technology--an evaluation.

This contribution compares a currently worn hearing instrument (i.e. R-HI) with a programmable multiband full-dynamic range compression behind-the-ear HI (i.e. T-HI), based on subject preference for HI, and, in addition, compares the preference for a linear/ non-linear amplification-mode (i.e. L-mode/C-mode). Finally, it evaluates some health technology aspects related to the devices. N = 34 experienced HI-users at a median age of 72 years (range 22-84) completed the trial, n = 5 being monaurally, and n = 29 being binaurally fitted. The trial comprises an unblinded comparative study of the R-HI and T-HI, in either C-mode or L-mode amplification, and a double-blind crossover study evaluating the C-mode versus the L-mode amplification. The results of the unblinded study showed that 94% (n = 32/34) preferred the T-HI, whereas two subjects preferred their current HI. The double-blind crossover study concerning the preference for the C-mode and L-mode, respectively, in the T-HI, showed that 72% (n = 23/32) had a significant preference for the non-linear amplification, whereas 28% (n = 9/32) preferred the linear amplification. Provided that the price of the T-HI is kept unchanged, a health technology evaluation may imply an estimate of 30 mill. DKR added costs on a national basis, which should be taken into account within the national hearing services.