Multiplex PCR of sonication fluid accurately differentiates between prosthetic joint infection and aseptic failure.

OBJECTIVE: Cultures have limited sensitivity in the diagnosis of prosthetic joint infection (PJI), especially in low-grade infections. We assessed the value of multiplex PCR in differentiating PJI from aseptic failure (AF). METHODS: Included were patients in whom the joint prosthesis was removed and submitted for sonication. The resulting sonication fluid was cultured and investigated by multiplex PCR, and compared with periprosthetic tissue culture. RESULTS: Among 86 explanted prostheses (56 knee, 25 hip, 3 elbow and 2 shoulder prostheses), AF was diagnosed in 62 cases (72%) and PJI in 24 cases (28%). PJI was more common detected by multiplex PCR (n=23, 96%) than by periprosthetic tissue (n=17, 71%, p=0.031) or sonication fluid culture (n=16, 67%, p=0.016). Among 12 patients with PJI who previously received antibiotics, periprosthetic tissue cultures were positive in 8 cases (67%), sonication fluid cultures in 6 cases (50%) and multiplex PCR in 11 cases (92%). In AF cases, periprosthetic tissue grew organisms in 11% and sonication fluid in 10%, whereas multiplex PCR detected no organisms. CONCLUSIONS: Multiplex PCR of sonication fluid demonstrated high sensitivity (96%) and specificity (100%) for diagnosing PJI, providing good discriminative power towards AF, especially in patients previously receiving antibiotics.

Iowa Medicaid Congestive Heart Failure Population Disease Management Demonstration, October 2006

Results from the Iowa Medicaid congestive heart failure population disease management demonstration confirm that a population and technology based remote monitoring platform can greatly reduce the need for costly acute care services by involving patients in their care, improving care effectiveness and promoting healthy behaviors.

Clinical picture of the amyloid arthropathy in patients with chronic renal failure maintained on haemodialysis using cellulose membranes.

The clinical picture of 15 patients (10 male, five female) with amyloid arthropathy secondary to chronic renal failure treated with haemodialysis has been studied. The average period of haemodialysis was 10.8 years. Joint symptoms appeared between three and 13 years after starting haemodialysis. No patient had renal amyloidosis. Early symptoms were varied and often overlapped: knee swelling (seven patients), painful and stiff shoulders (seven), and carpal tunnel syndrome (six) were the most prominent. Follow up showed extension to other joints. Joint effusions were generally of the non-inflammatory type. Radiologically, geodes and erosions of variable sizes were seen in the affected joints, which can develop into a destructive arthropathy. Amyloid was found in abdominal fat in three of the 12 patients on whom a needle aspiration was performed. Four of 12 patients showed changes compatible with amyloid infiltration in the echocardiogram. One patient had amyloid in the gastric muscular layer, another in the colon mucus, and two of four in rectal biopsy specimens. Amyloid deposits showed the presence of beta 2 microglobulin in 10 patients. The clinical and radiological picture was similar to the amyloid arthropathy associated with multiple myeloma. These patients can develop systemic amyloidosis.

Synovial fluid examination for the diagnosis of synovial amyloidosis in patients with chronic renal failure undergoing haemodialysis

The diagnosis of synovial amyloidosis is based upon synovial biopsy. Synovial fluid (SF) in seven patients with amyloid arthropathy associated with chronic renal failure undergoing haemodialysis were studied. The SF and synovial samples of 10 consecutive patients with seronegative mono- or oligoarthritis served as controls. Six of the seven patients with amyloid positive synovial biopsy specimens showed amyloid in their SF. No amyloid was found in the synovial tissue or fluid of the 10 patients in the control group, the sensitivity being 87.7%. The finding of amyloid in SF was highly reproducible, showing its presence in the same joint on several occasions. The deposits were Congophilia resistant to potassium permanganate pretreatment, and the immunohistochemical analysis proved that they contained beta 2 microglobulin. The high sensitivity and good reproducibility of the method shows that the finding of amyloid in SF is sufficient for the diagnosis of synovial amyloidosis. It is possible to perform immunohis

Amyloid arthropathy in patients undergoing periodical haemodialysis for chronic renal failure: a new complication.

Seven patients (five male and two female) with chronic renal failure (CRF) treated by periodical haemodialysis presented with swelling and effusion of more than three months' duration in knees (four bilateral), shoulders (two, one of them bilateral), elbow (one), and ankle (one). Four had a carpal tunnel syndrome both clinically and electromyographically (three bilateral). All patients had hyperparathyroidism secondary to their CRF, which was not due to amyloidosis in any of them. The dialysis duration period varied from five to 14 years, with an average of 8.6 years. Amyloid deposits (Congo red positive areas with green birefringence under polarising microscopy) were shown in six of the seven synovial biopsy specimens of the knee, in five of the sediments of the synovial fluids, and in specimens removed during carpal tunnel syndrome surgery. No amyloid was found in the biopsy specimen of abdominal fat of six of the patients. The finding of amyloid only in the synovial membrane and fluid, and carpal tunnel, its absence in abdominal fat, and the lack of other manifestations of generalised amyloidosis (cardiomyopathy, malabsorption syndrome, macroglossia, etc.) and of Bence Jones myeloma (protein immunoelectrophoresis normal) raises the possibility that this is a form of amyloidosis which is peculiar to CRF treated by periodical haemodialysis.

Possible synergism of physical exercise and ghrelin-agonists in patients with cachexia associated with chronic heart failure.

The occurrence of cachexia of multifactorial etiology in chronic heart failure (CHF) is a common and underestimated condition that usually leads to poor outcome and low survival rates, with high direct and indirect costs for the Health Care System. Recently, a consensus definition on cachexia has been reached, leading to a growing interest by the scientific community in this condition, which characterizes the last phase of many chronic diseases (i.e., cancer, acquired immunodeficiency syndrome). The etiology of cachexia is multifactorial and the underlying pathophysiological mechanisms are essentially the following: anorexia and malnourishment; immune overactivity and systemic inflammation; and endocrine disorders (anabolic/catabolic imbalance and resistance to growth hormone). In this paper, we review the main pathophysiological mechanisms underlying CHF cachexia, focusing also on the broad spectrum of actions of ghrelin and ghrelin agonists, and their possible use in combination with physical exercise to contrast CHF cachexia.

Viscoelasticity in Achilles Tendonopathy: Quantitative Assessment by Using Real-time Shear-Wave Elastography.

Purpose To investigate the differences in viscoelastic properties between normal and pathologic Achilles tendons ( AT Achilles tendon s) by using real-time shear-wave elastography ( SWE shear-wave elastography ). Materials and Methods The institutional review board approved this study, and written informed consent was obtained from 25 symptomatic patients and 80 volunteers. One hundred eighty ultrasonographic (US) and SWE shear-wave elastography studies of AT Achilles tendon s without tendonopathy and 30 studies of the middle portion of the AT Achilles tendon in patients with tendonopathy were assessed prospectively. Each study included data sets acquired at B-mode US (tendon morphology and cross-sectional area) and SWE shear-wave elastography (axial and sagittal mean velocity and relative anisotropic coefficient) for two passively mobilized ankle positions. The presence of AT Achilles tendon tears at B-mode US and signal-void areas at SWE shear-wave elastography were noted. Results Significantly lower mean velocity was shown in tendons with tendonopathy than in normal tendons in the relaxed position at axial SWE shear-wave elastography (P < .001) and in the stretched position at sagittal (P < .001) and axial (P = .0026) SWE shear-wave elastography . Tendon softening was a sign of tendonopathy in relaxed AT Achilles tendon s when the mean velocity was less than or equal to 4.06 m · sec(-1) at axial SWE shear-wave elastography (sensitivity, 54.2%; 95% confidence interval [ CI confidence interval ]: 32.8, 74.4; specificity, 91.5%; 95% CI confidence interval : 86.3, 95.1) and less than or equal to 5.70 m · sec(-1) at sagittal SWE shear-wave elastography (sensitivity, 41.7%; 95% CI confidence interval : 22.1, 63.3; specificity, 81.8%; 95% CI confidence interval : 75.3, 87.2) and in stretched AT Achilles tendon s, when the mean velocity was less than or equal to 4.86 m · sec(-1) at axial SWE shear-wave elastography (sensitivity, 66.7%; 95% CI confidence interval : 44.7, 84.3; specificity, 75.6%; 95% CI confidence interval : 68.5, 81.7) and less than or equal to 14.58 m · sec(-1) at sagittal SWE shear-wave elastography (sensitivity, 58.3%; 95% CI confidence interval : 36.7, 77.9; specificity, 83.5%; 95% CI confidence interval : 77.2, 88.7). Anisotropic results were not significantly different between normal and pathologic AT Achilles tendon s. Six of six (100%) partial-thickness tears appeared as signal-void areas at SWE shear-wave elastography . Conclusion Whether the AT Achilles tendon was relaxed or stretched, SWE shear-wave elastography helped to confirm and quantify pathologic tendon softening in patients with tendonopathy in the midportion of the AT Achilles tendon and did not reveal modifications of viscoelastic anisotropy in the tendon. Tendon softening assessed by using SWE shear-wave elastography appeared to be highly specific, but sensitivity was relatively low. © RSNA, 2014.

Procedure for human saphenous veins ex vivo perfusion and external reinforcement.

The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal hyperplasia (IH) that eventually leads to vessel occlusion and graft failure. Mechanical forces, particularly low shear stress and high wall tension, are thought to initiate and to sustain these cellular and molecular changes, but their exact contribution remains to be unraveled. To selectively evaluate the role of pressure and shear stress on the biology of IH, an ex vivo perfusion system (EVPS) was created to perfuse segments of human saphenous veins under arterial regimen (high shear stress and high pressure). Further technical innovations allowed the simultaneous perfusion of two segments from the same vein, one reinforced with an external mesh. Veins were harvested using a no-touch technique and immediately transferred to the laboratory for assembly in the EVPS. One segment of the freshly isolated vein was not perfused (control, day 0). The two others segments were perfused for up to 7 days, one being completely sheltered with a 4 mm (diameter) external mesh. The pressure, flow velocity, and pulse rate were continuously monitored and adjusted to mimic the hemodynamic conditions prevailing in the femoral artery. Upon completion of the perfusion, veins were dismounted and used for histological and molecular analysis. Under ex vivo conditions, high pressure perfusion (arterial, mean = 100 mm Hg) is sufficient to generate IH and remodeling of human veins. These alterations are reduced in the presence of an external polyester mesh.

Analysis of joint laxity after total ankle arthroplasty: cadaver study.

BACKGROUND: Clinical results of total ankle arthroplasty with early designs were disappointing. Recently-developed ankle prostheses have good mid-term results; however, limited information is available regarding effects of total ankle arthroplasty on ankle laxity. METHODS: Eight cadaveric lower extremities were tested with a custom device which enabled measurement of multi-axial forces, moments, and displacement during applied axial, shear, and rotational loading. Tests consisted of anterior-posterior and medial-lateral translation and internal-external rotation of the talus relative to the tibia during axial loads on the tibia simulating body weight (700 N) and an unloaded condition (5 N). Tests were performed in neutral, dorsiflexion, and plantarflexion. Laxity was determined for the intact ankle, and following insertion of an unconstrained total ankle implant, comparing load-displacement curve. FINDINGS: Laxity after total ankle arthroplasty did not approximate the normal ankle in most conditions tested. Displacement was significantly greater for total ankle arthroplasty in both posterior and lateral translation, and internal rotation, with 5 N axial loading, and anterior-posterior, medial-lateral translation, and internal-external rotation for 700 N axial loading. For the 700 N axial load condition, in the neutral ankle position, total anterior-posterior translation averaged 0.4 mm (SD 0.2 mm), but 6.0 mm (SD 1.5 mm) after total ankle arthroplasty (P<0.01). This study demonstrated more laxity in the replaced ankle than normal ankle for both unloaded and 700 N axially loaded conditions. INTERPRETATION: These data indicate the increased responsibility of the ligaments for ankle laxity after total ankle arthroplasty and suggest the importance of meticulous ligament reconstruction with total ankle arthroplasty operations.

Alignment of hexatic langmuir monolayers under shear

We have studied the structural changes that fatty acid monolayers in the Ov phase undergo when a simple shear flow is imposed. A strong coupling is revealed by the changes in domain structure that are observable using Brewster angle microscopy, suggesting the possibility of shear alignment. The dependence of the alignment on the molecular polar tilt proves that the mechanism is different than in nematic liquid crystals. We argue that the degenerate lattice symmetry lines of the underlying pseudohexagonal lattice align in the flow direction, and we explain the observed alignment angle using geometrical arguments.

Ex vivo Pulsatile Perfusion of Human Saphenous Veins Induces Intimal Hyperplasia and Increased Levels of the Plasminogen Activator Inhibitor 1.

Vessel wall trauma induces vascular remodeling processes including the development of intimal hyperplasia (IH). To assess the development of IH in human veins, we have used an ex vivo vein support system (EVVSS) allowing the perfusion of freshly isolated segments of saphenous veins in the presence of a pulsatile flow which reproduced arterial conditions regarding shear stress, flow rate and pressure during a period of 7 and 14 days. Compared to the corresponding freshly harvested human veins, histomorphometric analysis showed a significant increase in the intimal thickness which was already maximal after 7 days of perfusion. Expression of the endothelial marker CD31 demonstrated the presence of endothelium up to 14 days of perfusion. In our EVVSS model, the activity as well as the mRNA and protein expression levels of plasminogen activator inhibitor 1, the inhibitor of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), were increased after 7 days of perfusion, whereas the expression levels of tPA and uPA were not altered. No major change was observed between 7 and 14 days of perfusion. These data show that our newly developed EVVSS is a valuable setting to study ex vivo remodeling of human veins submitted to a pulsatile flow.

Bolus injections of synthetic atrial natriuretic peptide in patients with chronic renal failure or nephrotic syndrome.

The diuretic and natriuretic responses to exogenous synthetic atrial natriuretic peptide (ANP) were evaluated in patients with chronic renal failure (CRF) or nephrotic syndrome (NS). Patients were studied after an oral water load (8 ml/kg in CRF and 20 ml/kg in NS patients). A short intravenous bolus of either a placebo or ANP was administered when urine output was stable. In each group of patients, three doses of ANP were injected at 24 h intervals, i.e., 1.0, 1.5, and 2.0 micrograms/kg in the CRF and 1.0, 1.5, and 3.0 micrograms/kg in the NS group. Blood pressure and heart rate were monitored throughout the study and urinary volume and electrolyte excretion were measured every 20 min up to 3 h after the bolus. An acute and transient fall in blood pressure was observed immediately after the ANP injection. It was more pronounced in CRF than in NS patients. In CRF patients, ANP caused only a slight increase in urinary volume (13.5-44% over baseline) but a significant increase in urinary sodium excretion (45-114% over baseline). In NS patients, significant increases in both urine volume (60-105%) and sodium excretion (149-248%) were also found. In these latter patients, the renal response to ANP appeared to be better preserved. The hemodynamic and renal changes induced by ANP occurred mainly during the first 20 min following the ANP administration, when the peak plasma ANP levels were obtained. However, no clear dose-response effect could be evidenced in either group with the three doses of ANP chosen in this study.

Juxtaposition of melt impregnation and high-temperature shear zones in the upper mantle; field and petrological constraints from the Lanzo peridotite (Northern Italy)

Results of a field and microstructural study between the northern and the central bodies of the Lanzo plagioclase peridotite massif (NW Italy) indicate that the spatial distribution of deformation is asymmetric across kilometre-scale mantle shear zones. The southwestern part of the shear zone (footwall) shows a gradually increasing degree of deformation from porphyroclastic peridotites to mylonite, whereas the northeastern part (hanging wall) quickly grades into weakly deformed peridotites. Discordant gabbroic and basaltic dykes are asymmetrically distributed and far more abundant in the footwall of the shear zone. The porphyroclastic peridotite displays porphyroclastic zones and domains of igneous crystallization whereas mylonites are characterized by elongated porphyroclasts, embedded between fine-grained, polycrystalline bands of olivine, plagioclase, clinopyroxene, orthopyroxene, spinel, rare titanian pargasite, and domains of recrystallized olivine. Two types of melt impregnation textures have been found: (1) clinopyroxene porphyroclasts incongruently reacted with migrating melt to form orthopyroxene plagioclase; (2) olivine porphyroclasts are partially replaced by interstitial orthopyroxene. The meltrock reaction textures tend to disappear in the mylonites, indicating that deformation in the mylonite continued under subsolidus conditions. The pyroxene chemistry is correlated with grain size. High-Al pyroxene cores indicate high temperatures (11001030C), whereas low-Al neoblasts display lower final equilibration temperatures (860C). The spinel Cr-number [molar Cr/(Cr Al)] and TiO2 concentrations show extreme variability covering almost the entire range known from abyssal peridotites. The spinel compositions of porphyroclastic peridotites from the central body are more variable than spinel from mylonite, mylonite with ultra-mylonite bands, and porphyroclastic rocks of the northern body. The spinel compositions probably indicate disequilibrium and would favour rapid cooling, and a faster exhumation of the central peridotite body, relative to the northern one. Our results indicate that melt migration and high-temperature deformation are juxtaposed both in time and space. Meltrock reaction may have caused grain-size reduction, which in turn led to localization of deformation. It is likely that melt-lubricated, actively deforming peridotites acted as melt focusing zones, with permeabilities higher than the surrounding, less deformed peridotites. Later, under subsolidus conditions, pinning in polycrystalline bands in the mylonites inhibited substantial grain growth and led to permanent weak zones in the upper mantle peridotite, with a permeability that is lower than in the weakly deformed peridotites. Such an inversion in permeability might explain why actively deforming, fine-grained peridotite mylonite acted as a permeability barrier and why ascending mafic melts might terminate and crystallize as gabbros along actively deforming shear zones. Melt-lubricated mantle shear zones provide a mechanism for explaining the discontinuous distribution of gabbros in oceancontinent transition zones, oceanic core complexes and ultraslow-spreading ridges.

Termination of major ductile strike-slip shear and differential cooling along the Insubric line (Central Alps): U-Pb, Rb-Sr and 40Ar/39Ar ages of cross-cutting pegmatites

To constrain the age of strike-slip shear, related granitic magmatism, and cooling along the Insubric line, 29 size fractions of monazite and xenotime were dated by the U-Pb method, and a series of 25 Rb-Sr and Ar-40/Ar-39 ages were measured on different size fractions of muscovite and biotite. The three pegmatitic intrusions analyzed truncate high-grade metamorphic mylonite gneisses of the Simplon shear zone, a major Alpine structure produced in association with dextral strike-slip movements along the southern edge of the European plate, after collision with its Adriatic indenter. Pegmatites and aplites were produced between 29 and 25 Ma in direct relation to right-lateral shear along the Insubric line, by melting of continental crust having Sr-87/Sr-86 between 0.7199 and 0.7244 at the time of melting. High-temperature dextral strike-slip shear was active at 29.2 +/- 0.2 (2 sigma) Ma, and it terminated before 26.4 +/- 0.1 Ma. During dike injection, temperatures in the country rocks of the Isorno-Orselina and Monte Rosa structural units did not exceed approximate to 500 degrees C, leading to fast initial cooling, followed by slower cooling to approximate to 350 degrees C within several million years. In one case, initial cooling to approximate to 500 degrees C was significantly delayed by about 4 m.y., with final cooling to approximate to 300 degrees C at 20-19 Ma in all units. For the period between 29 and 19 Ma, cooling of the three sample localities was non-uniform in space and time, with significant variations on the kilometre scale. These differences are most likely due to strongly varying heat flow, and/or heterogeneous distribution of unroofing rates within the continuously deforming Insubric line. If entirely ascribed to differences in unroofing, corresponding rates would vary between 0.5 and 2.5 mm/y, for a thermal gradient of 30 degrees/km.

Robust accelerated failure time regression

Robust estimators for accelerated failure time models with asymmetric (or symmetric) error distribution and censored observations are proposed. It is assumed that the error model belongs to a log-location-scale family of distributions and that the mean response is the parameter of interest. Since scale is a main component of mean, scale is not treated as a nuisance parameter. A three steps procedure is proposed. In the first step, an initial high breakdown point S estimate is computed. In the second step, observations that are unlikely under the estimated model are rejected or down weighted. Finally, a weighted maximum likelihood estimate is computed. To define the estimates, functions of censored residuals are replaced by their estimated conditional expectation given that the response is larger than the observed censored value. The rejection rule in the second step is based on an adaptive cut-off that, asymptotically, does not reject any observation when the data are generat ed according to the model. Therefore, the final estimate attains full efficiency at the model, with respect to the maximum likelihood estimate, while maintaining the breakdown point of the initial estimator. Asymptotic results are provided. The new procedure is evaluated with the help of Monte Carlo simulations. Two examples with real data are discussed.