Jitter reduction using native fiducials in rotating mirror ultra-fast microphotography.

Rotating mirror cameras represent a workhorse technology for high speed imaging in the MHz framing regime. The technique requires that the target image be swept across a series of juxtaposed CCD sensors, via reflection from a rapidly rotating mirror. Employing multiple sensors in this fashion can lead to spatial jitter in the resultant video file, due to component misalignments along the individual optical paths to each CCD. Here, we highlight that static and dynamic fiducials can be exploited as an effective software-borne countermeasure to jitter, suppressing the standard deviation of the corrected file relative to the raw data by up to 88.5% maximally, and 66.5% on average over the available range of framing rates. Direct comparison with industry-standard algorithms demonstrated that our fiducial-based strategy is as effective at jitter reduction, but typically also leads to an aesthetically superior final form in the post-processed video files.

Mixing and matching causing taper wear: corrosion associated with pseudotumour formation.

We report a case of a male patient presenting with bilateral painful but apparently well-positioned and -fixed large-diameter metal-on-metal hip replacements four years post-operatively. Multiple imaging modes revealed a thick-walled, cystic expansile mass in communication with the hip joint (a pseudotumour). Implant retrieval analysis and tissue culture eliminated high bearing wear or infection as causes for the soft-tissue reaction, but noted marked corrosion of the modular neck taper adaptor and corrosion products in the tissues. Therefore, we believe corrosion products from the taper caused by mismatch of the implant components led to pseudotumour formation requiring revision.

Metal-on-metal hip resurfacing: a consensus from the Advanced Hip Resurfacing Course, Ghent, June 2009.

We report the consensus of surgical opinions of an international faculty of expert metal-on-metal hip resurfacing surgeons, with a combined experience of over 18,000 cases, covering required experience, indications, surgical technique, rehabilitation and the management of problematic cases.

Thermal spread and heat absorbance differences between open and laparoscopic surgeries during energized dissections by electrosurgical instruments.

BACKGROUND: The reported literature suggests a higher incidence of collateral damage during energized dissections in laparoscopic surgery than in open surgery, probably because the ambient environment of the two approaches causes different heat absorbance and thermal spread during energized dissection. METHODS: The experimental design involved randomized allocation of the surgical approach (4 open and 4 laparoscopic procedures) for eight adult pigs. A bipolar electrosurgery system (LigaSure) was used to perform 40 standardized regional dissections and procedures (5 per animal in randomized order). During these procedures, both white light and infrared thermographic imaging (3-5 mum) were recorded, and biopsy specimens were procured for histology. RESULTS: The core body temperatures were significantly different between the two approaches. The laparoscopic group had a smaller temperature drop (3.08 +/- 0.98 degrees C vs 1.9 +/- 0.72 degrees C; p = 0.03). Differences also were observed in the thermal spread between the laparoscopic and open groups during portal vein dissection with the Advance (1.7 +/- 0.2 mm vs 2.3 +/- 1.7 mm; p = 0.07). Both thermography and histology confirmed the safety of the LigaSure system in limiting thermal spread and necrosis at the fusion line. Significant degradation of the instruments began after 10 activations. The deterioration was faster and more extensive in laparoscopic surgery. CONCLUSIONS: Heat absorbance and thermal spread during bipolar electrosurgery are significantly different between open and laparoscopic surgery. Device performance degradation with repeat activations is more marked in laparoscopic surgery.

Correlation between inclination of the acetabular component and metal ion levels in metal-on-metal hip resurfacing replacement.

We examined the relationships between the serum levels of chromium and cobalt ions and the inclination angle of the acetabular component and the level of activity in 214 patients implanted with a metal-on-metal resurfacing hip replacement. Each patient had a single resurfacing and no other metal in their body. All serum measurements were performed at a minimum of one year after operation. The inclination of the acetabular component was considered to be steep if the abduction angle was greater than 55 degrees. There were significantly higher levels of metal ions in patients with steeply-inclined components (p = 0.002 for chromium, p = 0.003 for cobalt), but no correlation was found between the level of activity and the concentration of metal ions. A highly significant (p < 0.001) correlation with the arc of cover was found. Arcs of cover of less than 10 mm were correlated with a greater risk of high concentrations of serum metal ions. The arc of coverage was also related to the design of the component and to size as well as to the abduction angle of the acetabular component. Steeply-inclined acetabular components, with abduction angles greater than 55 degrees, combined with a small size of component are likely to give rise to higher serum levels of cobalt and chromium ions. This is probably due to a greater risk of edge-loading.

Revision of metal-on-metal resurfacing arthroplasty of the hip: the influence of malpositioning of the components.

We have reviewed 42 patients who had revision of metal-on-metal resurfacing procedures, mostly because of problems with the acetabular component. The revisions were carried out a mean of 26.2 months (1 to 76) after the initial operation and most of the patients (30) were female. Malpositioning of the acetabular component resulted in 27 revisions, mostly because of excessive abduction (mean 69.9 degrees ; 56 degrees to 98 degrees ) or insufficient or excessive anteversion. Seven patients had more than one reason for revision. The mean increase in the diameter of the component was 1.8 mm (0 to 4) when exchange was needed. Malpositioning of the components was associated with metallosis and a high level of serum ions. The results of revision of the femoral component to a component with a modular head were excellent, but four patients had dislocation after revision and four required a further revision.

Observing ultrasound stimulated microbubble dynamics at MHz framing rates.

Microbubble contrast agents were originally developed to enhance echogenicity in diagnostic sonography. However, their somewhat unique acoustic response and facility to transduct energy into spatially focussed regimes, together with the clinical demand for non-invasive adjuncts and options to conventional therapy, have seen interest in exploring the therapeutic potential of microbubbbles grow steadily within this past decade. For the purposes of the present study, we examined the ultrasonically stimulated response of many such microbubbles by controlling their spatial placement with bespoke optical traps. The objective was to improve our understanding of their statistical behaviour and to feed this information into realistic computational models so that processes might be more easily optimised. Hence, individual microbubbles of commercial [low-index] ultrasound contrast agent were isolated from a parent population by selection using a Laguerre-Gaussian optical trap, and subsequently manipulated to controllable micrometer level displacements from a solid surface. This configuration was then insonated using a 60ms burst of 1MHz ultrasound at a nominal peak pressure of 6.5MPa, and the subsequent bubble dynamics recorded using ultra high speed micro-photography at microsecond temporal resolutions. Any resultant damage induced at the target surface was also observed and characterised using atomic force microscopy.

Breath-figure polymer films with local microporosity controlled via spatio-thermal templating.

Porous structures offer a vast range of important industrial applications. In the context of medicine, and specifically in the area of controlled drug delivery, spatial [and temporal] control over local porosity has a significant influence on net molecular flux through [membrane-based] controlled release platforms. Such systems may be formulated as oral, transdermal, or even implantable entities, and address chronic infusion needs covering such ailments as diabetes, cancer and hypertension [1]. In all the aforementioned situations, a facility to spatially control porosity could offer significant advantage, such as safer controlled release over extended durations. Here, we describe a novel route to engineering-in such flexibility within polymeric thin films by modifying spin-coating protocols to accommodate breath film patterning, that is, the spatially controlled condensation of pore forming droplets onto a liquid-polymer film. Upon film solidification, characterization via optical- and scanning probe microscopy revealed that local variations in porosity, as inferred from topographic measurements, could be effectively controlled through provision of an embossed vacuum holding chuck that effectively retains intimate thermal contact with the film substrate during forming. Parallel measurements using real time thermography support the hypothesis that porosity is controlled by local solvent evaporation rates.

Reduction of the potential for thermal damage during hip resurfacing.

Resurfacing arthroplasty of the hip is being used increasingly as an alternative to total hip replacement, especially for young active patients. There is concern about necrosis of the femoral head after resurfacing which can result in fracture and loosening. Most systems use a cemented femoral component, with the potential for thermal necrosis of the cancellous bone of the reamed femoral head. We used thermal probes to record temperatures close to the cement-bone interface during resurfacing arthroplasty. The maximum temperature recorded at the cement-bone interface in four cases was approximately 68 degrees C which was higher than that reported to kill osteocytes. A modified surgical technique using insertion of a suction cannula into the lesser trochanter, generous pulsed lavage and early reduction of the joint significantly reduced the maximum recorded cancellous bone temperature to approximately 36 degrees C in five cases (p = 0.014). We recommend the modified technique since it significantly reduces temperatures at the cement-bone interface.

Wear particles from metal-on-metal total hip replacements: effects of implant design and implantation time.

Detailed characterization of wear particles is necessary to understand better the implant wear mechanisms and the periprosthetic tissue response. The purposes of the present study were to compare particle characteristics of current with older designs of metal-on-metal (MM) total hip replacements (THRs), and to determine the effect of implantation time on wear particle characteristics. Metal wear particles isolated from periprosthetic tissues from 19 patients with MM THRs of current and older designs and at different implantation times (very short, longer, and very long) were studied using transmission electron microscopy and energy dispersive X-ray analysis. The particles from the current design implants with implantation times of not more than 15 months (very short-term) were almost exclusively round to oval chromium oxide particles. In all other cases, although the predominance was still round to oval chromium oxide particles, greater proportions of cobalt-chromium-molybdenum (Co-Cr-Mo) particles, mainly needle-shaped, were detected. Very long-term THRs implanted for more than 20 years had the highest percentage of needle-shaped Co-Cr-Mo particles. Particle lengths were not markedly different between the different designs and implantation times except for the current design implants of not more than 15 months, which had a significantly smaller mean length of 39 nm. In conclusion, the implant design did not seem to have a significant influence on particle characteristics whereas the implantation time appeared to have the most effect on the particles. It should be noted that, because of the limited number of tissue retrievals available, some uncertainty remains regarding the generality of these findings.

Notching of the femoral neck during resurfacing arthroplasty of the hip: a vascular study.

During hip resurfacing arthroplasty, excessive valgus positioning or surgical technique can result in notching of the femoral neck. Although mechanical weakening and subsequent fracture of the femoral neck are well described, the potential damage to the retinacular vessels leading to an ischaemic event is relatively unknown. Using laser Doppler flowmetry, we measured the blood flow in 14 osteoarthritic femoral heads during routine total hip replacement surgery, before and after notching of the femoral neck. In ten hips there was a reduction in blood flow of more than 50% from the baseline value after simulated notching of the femoral neck. Our results suggest that femoral head vascularity in the osteoarthritic state is similar to the non-arthritic state, where damage to the extraosseous vessels can predispose to avascular necrosis. Surgeons who perform resurfacing arthroplasty of the hip should pay careful attention to these vessels by avoiding excessive dissection around the femoral neck and/or notching.

Skin wound closure with a novel shape-memory alloy fixator.

BACKGROUND: Previously, we have described novel, thermally deployable tissue fixators based on the shape-memory properties of nickel titanium. The present study reports on the in vivo wound closure with these fixators as a preliminary to evaluating their use for bowel anastomoses. METHODS: Twenty adult Sprague-Dawley rats had 2.0-cm dorsal skin incisions approximated either with shape-memory alloy (SMA) fixators or conventional skin staples on a random basis. Electrical resistance heating was used to transform and deploy the SMA fixators into the wound. The rats were killed on day 14 or day 28 and wound specimens were harvested for force distraction studies and histologic examination. RESULTS: There was no incidence of wound dehiscence. 14- and 28-day wounds from both groups showed no significant difference in breaking force or energy. Histology revealed appropriate stages of wound healing for both SMA-closed and control wounds. CONCLUSIONS: The results confirm the efficacy and safety of tissue-edge approximation with SMA fixators.

An unusual lymphocytic perivascular infiltration in tissues around contemporary metal-on-metal joint replacements.

BACKGROUND: Metal-on-metal bearing surfaces have been reintroduced for use during total hip replacement. To assess tissue reactions to various types of articulations, we studied the histological appearance of periprosthetic tissues retrieved from around metal-on-metal and metal-on-polyethylene total hip replacements and compared these findings with the appearance of control tissues retrieved at the time of primary arthroplasty. METHODS: Periprosthetic tissues were obtained at the time of revision of twenty-five cobalt chromium-on-cobalt chromium, nine cobalt chromium-on-polyethylene, and ten titanium-on-polyethylene total hip arthroplasties. Control tissues were obtained from nine osteoarthritic hips at the time of primary total hip arthroplasty. Each tissue sample was processed for routine histological analysis, and sections were stained with hematoxylin and eosin. Quantitative stereological analysis was performed with use of light microscopy. RESULTS: Tissue samples obtained from hips with metal-on-metal implants displayed a pattern of well-demarcated tissue layers. A prominent feature, seen in seventeen of twenty-five tissue samples, was a pattern of perivascular infiltration of lymphocytes. In ten of the tissue samples obtained from hips with metal-on-metal prostheses, there was also an accumulation of plasma cells in association with macrophages that contained metallic wear-debris particles. The surfaces of tissues obtained from hips with metal-on-metal prostheses were more ulcerated than those obtained from hips with other types of implants, particularly in the region immediately superficial to areas of perivascular lymphocytic infiltration. The lymphocytic infiltration was more pronounced in samples obtained at the time of revision because of aseptic failure than in samples retrieved at the time of autopsy or during arthrotomy for reasons other than aseptic failure. Total-joint-replacement and surface-replacement designs of metal-on-metal prostheses were associated with similar results. Tissue samples obtained from hips with metal-on-polyethylene implants showed far less surface ulceration, much less distinction between tissue layers, no pattern of lymphocytic infiltration, and no plasma cells. The inflammation was predominantly histiocytic. Tissues retrieved from hips undergoing primary joint replacement showed dense scar tissue and minimal inflammation. CONCLUSIONS AND CLINICAL RELEVANCE: The pattern and type of inflammation seen in periprosthetic tissues obtained from hips with metal-on-metal and metal-on-polyethylene implants are very different. At the present time, we do not know the prevalence or clinical implications of these histologic findings, but we suggest that they may represent a novel mode of failure for some metal-on-metal joint replacements.

Papillary urothelial neoplasm of low malignant potential: reliability of diagnosis and outcome.

OBJECTIVE: To determine the ability of pathologists to reproducibly diagnose a newly defined lesion, i.e. the papillary urothelial neoplasm of low malignant potential (PUNLMP) using the published criteria, defined by the 1998 World Health Organisation/International Society of Urological Pathology (WHO/ISUP) classification system; in addition, debate remains about the clinical behaviour of these lesions, thus the rates of recurrence and progression of PUNLMP lesions were assessed and compared with low-grade papillary urothelial carcinomas (LG-PUC) and high-grade (HG-PUC) over a 10-year follow-up. PATIENTS AND METHODS: Forty-nine cases of superficial bladder cancer (G1-3 pTa) representing an initial diagnosis of transitional cell carcinoma made in 1990 were identified and re-graded using the 1998 WHO/ISUP classification by two pathologists. Inter-observer agreement was assessed using Cohen weighted kappa statistics. After re-classification the clinical follow-up was reviewed retrospectively, and episodes of recurrence and progression recorded. RESULTS: The inter-observer agreement was moderate, regardless of whether one (kappa 0.45) or two (kappa 0.60) pathologists were used to grade these lesions. Re-classification identified 12 PUNLMP, 28 LG-PUC and nine HG-PUC. PUNLMP lesions recurred in 25% (3/12) of cases; no progression was documented. Recurrence rates were 75% (21/28) and 67% (6/9) for LG- and HG-PUC, respectively, and progression rates were 4% (1/28) and 22% (2/9). CONCLUSION: The 1998 WHO/ISUP classification of urothelial neoplasms can be reproducibly applied by pathologists, with a moderate level of agreement. There is evidence that PUNLMP lesions have a more indolent clinical behaviour than urothelial carcinomas. However, the risk of recurrence and progression remains, and clinical monitoring of these patients is important.

Real-time thermography during energized vessel sealing and dissection.

BACKGROUND: Energized dissection systems facilitate laparoscopic dissection and hemostasis and reduce instrument traffic. However, they can introduce undesirable thermal collateral/proximity damage to adjacent structures mainly by heat conduction, although other mechanisms may be involved. The latest generation devices have the potential to reduce the incidence of such problems through use of active feedback control over the power output. This effectively regulates the delivery of energy to the target tissue with minimal thermal collateral damage. In addition, innovative heat-sink engineering of the device head ensures that the surface of the instrument tip remains cool (<45 degrees C). In this study, we evaluated the performance of this technology (LigaSure) by using dynamic infrared thermography. The thermal imaging measurements were then correlated with histopathologic studies. The overall value of in situ thermography as an adjunct to energized surgical dissection systems was also assessed. METHODS: Eight anesthetized pigs underwent open surgery to mobilize eight target vessels/organs in a randomized fashion. The LigaSure vessel sealing system with Instant Response Technology was used with three different interchangeable heads. In situ dynamic thermography was undertaken with a thermal imaging camera operating in the mid-infrared (3-5 microm) waveband and with each fully digitized 12-bit thermographic frame acquired at a rate of 60 Hz. Following sacrifice at the end of the dissection, tissue from the dissected regions was harvested for histology by an independent pathologist who was blinded to the thermographic data. RESULTS: Seals made with both the LS1000 5-mm laparoscopic head (predominantly to the small bowel and colon) and the LS1100 10-mm (Atlas) device (on the liver and short gastric tissues) were outwardly satisfactory. The average thermal spread [see text] with the LS1000 was = [see text] 4.4 mm, and the exposed surface of the instrument tip developed a temperature of approximately 100 degrees C. This instrument thus has the potential, albeit small, for heat-related proximity iatrogenic injury. The more technologically advanced LS1100 10-mm laparoscopic instrument exhibited a superior performance, with [see text] = 1.8 mm, and with a maximal temperature on the exposed surface of the jaws well within tolerable limits (approximately 35 degrees C) for use during surgery (laparoscopic or open). This was confirmed by histological studies that demonstrated negligible evidence of thermal damage. CONCLUSIONS: In situ thermal imaging represents a powerful modality for the monitoring of energized dissection/coagulation during surgery. The LigaSure system used with the LS1100 head constitutes a very safe option for energized dissection and hemostasis of vessels with a diameter of up to approximately 7 mm.

Polyethylene wear characteristics in vivo and in a knee stimulator.

Validation of a wear simulator requires that the device produce a similar type and amount of wear and particles of a comparable morphology as occurs clinically. Using techniques previously established to compare polyethylene particles from hip simulators to those from retrieved tissues, particles isolated from six revised posterior stabilized knee replacements were characterized and compared to particles generated from the same knee design worn in a knee simulator. The particles produced in the knee simulator were of comparable size but had less variability in their form factor compared to the particles produced in vivo. Comparable wear features were seen on the articulating surfaces in both groups. These results indicate that this knee joint simulator is able to reproduce a baseline type of wear that is similar to that in vivo and should encourage further use of this device to better understand knee component wear and function.

The effect of contact area on wear in relation to fixed bearing and mobile bearing knee replacements.

It is generally assumed that the wear rates in knee replacements are reduced as the contact area is increased. Hence, fixed bearing or mobile bearing designs with large contact areas throughout the full range of flexion wear less than partially conforming fixed-bearing designs. This hypothesis was investigated in an experimental model, where flat-ended ultra high molecular weight polyethylene pins of varying diameters were reciprocated and rotated on polished metal plates under a constant load with serum lubrication. The pin diameters ranged from 8-23 mm, giving nominal contact pressures from 23.9-2.8 MPa, covering the range associated with a wide spectrum of total knees including mobile-bearings. For pin diameters of 8-12 mm, the mean wear rates were in the range of 5.0-16.0 E-10 g/cycle. For diameters of 17 and 23 mm, the mean wear rates were approximately 1.0 E-10 g/cycle. The latter wear rates were significantly less than the former. Scanning electron microscopy indicated milder wear processes with the larger diameters, while the smaller diameters exhibited transverse ripples and cracks and detachment of thin layers from the surface. The percentages of granules (mostly submicron), fibrils and flakes, and the sizes of these particle types were similar among all pin diameters, except that, for the 23 mm pin diameter, the percentage of fibrils increased and of flakes decreased. This work supports the hypothesis that larger contact areas, up to the maximum area tested in our study, produce lower wear rates, and suggests that there is no disadvantage regarding particle type or size associated with the larger areas of contact.

Measurement of bacterial ingestion and killing by macrophages.

This unit presents fairly simple assays for measuring the binding of bacteria to macrophages, internalization of bacteria (also called ingestion or phagocytosis), and bacterial killing by macrophages. The first basic protocol describes how to measure the ability of macrophages to ingest bacteria. Because it is critical to remove residual extracellular organisms, the protocol presents two alternative steps to accomplish this: a washing procedure and a more stringent method in which cells are sedimented through sucrose. In addition, it is important to distinguish those bacteria truly ingested by a macrophage from those that are bound to, but not internalized by, the cell. A simple but effective way to do this is described in an alternate protocol. The unit also presents two ways to measure the ability of a macrophage to kill bacteria it has internalized. The first is a straightforward assay in which bacterial colonies are enumerated before and after a killing period; a subsequent colony count will indicate whether the bacteria grew within or were killed by the macrophage. The second protocol describes a way to measure bacterial viability based on bacterial metabolism, in which the ability of bacterial dehydrogenases to mediate the reduction of a tetrazolium salt to purple formazan is monitored by measuring absorbance spectrophotometrically.

Doxorubicin-resistant variants of human prostate cancer cell lines DU 145, PC-3, PPC-1, and TSU-PR1: characterization of biochemical determinants of antineoplastic drug sensitivity.

Intrinsic and acquired antineoplastic drug resistance remain a major problem for advanced prostate cancer treatment. In order to characterize mechanisms of anti-neoplastic drug resistance in human prostate cancer cell lines, resistant sublines of four of the commonly studied prostate cancer cell lines (DU 145, PC-3, PPC-1, and TSU-PR1) were selected following exposure to increasing concentrations of doxorubicin (from 10-1000 nM). Sensitivity patterns of the parent and doxorubicin-resistant sublines to various anti-neoplastic drugs, including adriamycin, amsacrine, etoposide, camptothecin, vinblastine, vincristine, fluorodeoxyuridine, and melphalan, were determined using a sulforhodamine B growth inhibition assay. The expression of three well-described antineoplastic drug resistance proteins, P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and lung resistance protein (LRP), was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) assays specific for each of the mRNA species, and using immunocytochemical staining procedures specific for each of the polypeptides. All four of the doxorubicin-selected prostate cancer cell lines exhibited a multidrug resistance phenotype; administration of verapamil restored doxorubicin sensitivity for each of the drug resistant sublines. Although significant MDR1 expression was not detected in any of the parent cell lines before drug exposure by RT-PCR analysis or by immunocytochemistry, both MDR1 mRNA and P-gp protein were expressed by the TSU-PR1 Adr 1000 subline. In contrast, MRP mRNA and protein were present in each of the prostate cancer cell lines before doxorubicin-selection, and an increase in MRP expression appeared to accompany the acquisition of drug resistance in DU 145, PC-3, and PPC-1 doxorubicin-resistant sublines. LRP was variably expressed by each of the parent and resistant cell lines. These data suggest that drug resistance in human prostate cancer may be multifactorial, with MRP and LRP frequently expressed in prostate cancer cells before antineoplastic drug treatment and P-gp expression occasionally acquired after drug exposure.