Benefit of Cup Medialization in Total Hip Arthroplasty is Associated With Femoral Anatomy.

BACKGROUND: Medialization of the cup with a respective increase in femoral offset has been proposed in THA to increase abductor moment arms. Insofar as there are potential disadvantages to cup medialization, it is important to ascertain whether the purported biomechanical benefits of cup medialization are large enough to warrant the downsides; to date, studies regarding this question have disagreed. QUESTIONS/PURPOSES: The purpose of this study was to quantify the effect of cup medialization with a compensatory increase in femoral offset compared with anatomic reconstruction for patients undergoing THA. We tested the hypothesis that there is a (linear) correlation between preoperative anatomic parameters and muscle moment arm increase caused by cup medialization. METHODS: Fifteen patients undergoing THA were selected, covering a typical range of preoperative femoral offsets. For each patient, a finite element model was built based on a preoperative CT scan. The model included the pelvis, femur, gluteus minimus, medius, and maximus. Two reconstructions were compared: (1) anatomic position of the acetabular center of rotation, and (2) cup medialization compensated by an increase in the femoral offset. Passive abduction-adduction and flexion-extension were simulated in the range of normal gait. Muscle moment arms were evaluated and correlated to preoperative femoral offset, acetabular offset, height of the greater trochanter (relative to femoral center of rotation), and femoral antetorsion angle. RESULTS: The increase of muscle moment arms caused by cup medialization varied among patients. Muscle moment arms increase by 10% to 85% of the amount of cup medialization for abduction-adduction and from -35% (decrease) to 50% for flexion-extension. The change in moment arm was inversely correlated (R(2) = 0.588, p = 0.001) to femoral antetorsion (anteversion), such that patients with less femoral antetorsion gained more in terms of hip muscle moments. No linear correlation was observed between changes in moment arm and other preoperative parameters in this series. CONCLUSIONS: The benefit of cup medialization is variable and depends on the individual anatomy. CLINICAL RELEVANCE: Cup medialization with compensatory increase of the femoral offset may be particularly effective in patients with less femoral antetorsion. However, cup medialization must be balanced against its tradeoffs, including the additional loss of medial acetabular bone stock, and eventual proprioceptive implications of the nonanatomic center of rotation and perhaps joint reaction forces. Clinical studies should better determine the relevance of small changes of moment arms on function and joint reaction forces.

Comparisons of preoperative three-dimensional planning and surgical reconstruction in primary cementless total hip arthroplasty.

Reconstruction of important parameters such as femoral offset and torsion is inaccurate, when templating is based on plain x-rays. We evaluate intraoperative reproducibility of pre-operative CT-based 3D-templating in a consecutive series of 50 patients undergoing primary cementless THA through an anterior approach. Pre-operative planning was compared to a postoperative CT scan by image fusion. The implant size was correctly predicted in 100% of the stems, 94% of the cups and 88% of the heads (length). The difference between the planned and the postoperative leg length was 0.3 + 2.3 mm. Values for overall offset, femoral anteversion, cup inclination and anteversion were 1.4 mm ± 3.1, 0.6° ± 3.3°, -0.4° ± 5° and 6.9° ± 11.4°, respectively. This planning allows accurate implant size prediction. Stem position and cup inclination are accurately reproducible.

Proteomic analysis of peach fruit mesocarp softening and chilling injury using difference gel electrophoresis (DIGE)

Background: Peach fruit undergoes a rapid softening process that involves a number of metabolic changes. Storing fruit at low temperatures has been widely used to extend its postharvest life. However, this leads to undesired changes, such as mealiness and browning, which affect the quality of the fruit. In this study, a 2-D DIGE approach was designed to screen for differentially accumulated proteins in peach fruit during normal softening as well as under conditions that led to fruit chilling injury. Results:The analysis allowed us to identify 43 spots -representing about 18% of the total number analyzed- that show statistically significant changes. Thirty-nine of the proteins could be identified by mass spectrometry. Some of the proteins that changed during postharvest had been related to peach fruit ripening and cold stress in the past. However, we identified other proteins that had not been linked to these processes. A graphical display of the relationship between the differentially accumulated proteins was obtained using pairwise average-linkage cluster analysis and principal component analysis. Proteins such as endopolygalacturonase, catalase, NADP-dependent isocitrate dehydrogenase, pectin methylesterase and dehydrins were found to be very important for distinguishing between healthy and chill injured fruit. A categorization of the differentially accumulated proteins was performed using Gene Ontology annotation. The results showed that the 'response to stress', 'cellular homeostasis', 'metabolism of carbohydrates' and 'amino acid metabolism' biological processes were affected the most during the postharvest. Conclusions: Using a comparative proteomic approach with 2-D DIGE allowed us to identify proteins that showed stage-specific changes in their accumulation pattern. Several proteins that are related to response to stress, cellular homeostasis, cellular component organization and carbohydrate metabolism were detected as being differentially accumulated. Finally, a significant proportion of the proteins identified had not been associated with softening, cold storage or chilling injury-altered fruit before; thus, comparative proteomics has proven to be a valuable tool for understanding fruit softening and postharvest.

In vitro effect of malachite green on Candida albicans involves multiple pathways and transcriptional regulators UPC2 and STP2.

In this study, we show that a chemical dye, malachite green (MG), which is commonly used in the fish industry as an antifungal, antiparasitic, and antibacterial agent, could effectively kill Candida albicans and non-C. albicans species. We have demonstrated that Candida cells are susceptible to MG at a very low concentration (MIC that reduces growth by 50% [MIC(50)], 100 ng ml(-1)) and that the effect of MG is independent of known antifungal targets, such as ergosterol metabolism and major drug efflux pump proteins. Transcriptional profiling in response to MG treatment of C. albicans cells revealed that of a total of 207 responsive genes, 167 genes involved in oxidative stress, virulence, carbohydrate metabolism, heat shock, amino acid metabolism, etc., were upregulated, while 37 genes involved in iron acquisition, filamentous growth, mitochondrial respiration, etc., were downregulated. We confirmed experimentally that Candida cells exposed to MG resort to a fermentative mode of metabolism, perhaps due to defective respiration. In addition, we showed that MG triggers depletion of intracellular iron pools and enhances reactive oxygen species (ROS) levels. These effects could be reversed by the addition of iron or antioxidants, respectively. We provided evidence that the antifungal effect of MG is exerted through the transcription regulators UPC2 (regulating ergosterol biosynthesis and azole resistance) and STP2 (regulating amino acid permease genes). Taken together, our transcriptome, genetic, and biochemical results allowed us to decipher the multiple mechanisms by which MG exerts its anti-Candida effects, leading to a metabolic shift toward fermentation, increased generation of ROS, labile iron deprivation, and cell necrosis.

Direct detection of a BRAF mutation in total RNA from melanoma cells using cantilever arrays.

Malignant melanoma, the deadliest form of skin cancer, is characterized by a predominant mutation in the BRAF gene. Drugs that target tumours carrying this mutation have recently entered the clinic. Accordingly, patients are routinely screened for mutations in this gene to determine whether they can benefit from this type of treatment. The current gold standard for mutation screening uses real-time polymerase chain reaction and sequencing methods. Here we show that an assay based on microcantilever arrays can detect the mutation nanomechanically without amplification in total RNA samples isolated from melanoma cells. The assay is based on a BRAF-specific oligonucleotide probe. We detected mutant BRAF at a concentration of 500 pM in a 50-fold excess of the wild-type sequence. The method was able to distinguish melanoma cells carrying the mutation from wild-type cells using as little as 20 ng µl(-1) of RNA material, without prior PCR amplification and use of labels.

Total knee arthroplasty - a clinical and numerical study of the micromovements of the tibial implant

Introduction The importance of the micromovements in the mechanism of aseptic loosening is clinically difficult to evaluate. To complete the analysis of a series of total knee arthroplasties (TKA), we used a tridimensional numerical model to study the micromovements of the tibial implant.Material and Methods Fifty one patients (with 57 cemented Porous Coated Anatomic TKAs) were reviewed (mean follow-up 4.5 year). Radiolucency at the tibial bone-cement interface was sought on the AP radiographs and divided in 7 areas. The distribution of the radiolucency was then correlated with the axis of the lower limb as measured on the orthoradiograms.The tridimensional numerical model is based on the finite element method. It allowed the measurement of the cemented prosthetic tibial implant's displacements and the microvements generated at bone-ciment interface. A total load (2000 Newton) was applied at first vertically and asymetrically on the tibial plateau, thereby simulating an axial deviation of the lower limbs. The vector's posterior inclination then permitted the addition of a tangential component to the axial load. This type of effort is generated by complex biomechanical phenomena such as knee flexion.Results 81 per cent of the 57 knees had a radiolucent line of at least 1 mm, at one or more of the tibial cement-epiphysis jonctional areas. The distribution of these lucent lines showed that they came out more frequently at the periphery of the implant. The lucent lines appeared most often under the unloaded margin of the tibial plateau, when axial deviation of lower limbs was present.Numerical simulations showed that asymetrical loading on the tibial plateau induced a subsidence of the loaded margin (0-100 microns) and lifting off at the opposite border (0-70 microns). The postero-anterior tangential component induced an anterior displacement of the tibial implant (160-220 microns), and horizontal micromovements with non homogenous distribution at the bone-ciment interface (28-54 microns).Discussion Comparison of clinical and numerical results showed a relation between the development of radiolucent lines and the unloading of the tibial implant's margin. The deleterious effect of lower limbs' axial deviation is thereby proven. The irregular distribution of lucent lines under the tibial plateau was similar of the micromovements' repartition at the bone-cement interface when tangential forces were present. A causative relation between the two phenomenaes could not however be established.Numerical simulation is a truly useful method of study; it permits to calculate micromovements which are relative, non homogenous and of very low amplitude. However, comparative clinical studies remain as essential to ensure the credibility of results.

The effect of femoral component rotation on the five-year outcome of cemented mobile bearing total knee arthroplasty.

PURPOSE: Performing total knee replacement, accurate alignment and neutral rotation of the femoral component are widely believed to be crucial for the ultimate success. Contrary to absolute bone referenced alignment, using a ligament balancing technique does not automatically rotate the femoral component parallel to the transepicondylar axis. In this context we established the hypothesis that rotational alignment of the femoral component parallel to the transepicondylar axis (0° ± 3°) results in better outcome than alignment outside of this range. METHODS: We analysed 204 primary cemented mobile bearing total knee replacements five years postoperatively. Femoral component rotation was measured on axial radiographs using the condylar twist angle (CTA). Knee society score, range of motion as well as subjective rating documented outcome. RESULTS: In 96 knees the femoral component rotation was within the range 0 ± 3° (neutral rotation group), and in 108 knees the five-year postoperative rotational alignment of the femoral component was outside of this range (outlier group). Postoperative CTA showed a mean of 2.8° (±3.4°) internal rotation (IR) with a range between 6° external rotation (ER) and 15° IR (CI 95). No difference with regard to subjective and objective outcome could be detected. CONCLUSION: The present work shows that there is a large given natural variability in optimal rotational orientation, in this study between 6° ER and 15° IR, with numerous co-factors determining correct positioning of the femoral component. Further studies substantiating pre- and postoperative determinants are required to complete the understanding of resulting biomechanics in primary TKA.

Role of CD44H carbohydrate structure in neuroblastoma adhesive properties.

BACKGROUND: CD44 represents a heterogeneous group of surface glycoproteins involved in cell-cell and cell-matrix interactions. CD44H is the major receptor for hyaluronate, and most if not all CD44H known functions are attributed to its ability to recognize hyaluronate. We have previously demonstrated a lack of CD44 expression in high stages and NMYC-amplified tumors and further have shown that NMYC-amplified cell lines either did not express CD44 at all or expressed a nonfunctional receptor. On the other hand, nonamplified cells constitutively expressed an active receptor, suggesting that absence of CD44-mediated hy aluronate binding could be related to increased malignancy in human neuroblastoma. PROCEDURE: In the present study we have compared the glycosylated structure of CD44 expressed by NMYC amplified vs. nonamplified cell lines in relation to their adhesive properties for hyaluronate. These adhesive properties were measured after modifications of the carbohydrate structure with enzymes and inhibitors of N- or O-linked glycosylation. RESULTS AND CONCLUSIONS: Our results indicate that increased sialylation, defective N-linked glycosylation, and substitution of the CD44 glycoprotein with keratan sulfate glycosaminoglycan might include modifications observed on neuroblastoma cells that could account for the inability of the receptor to bind hyaluronate.

Effects of lactate on glucose metabolism in healthy subjects and in severely injured hyperglycemic patients.

Hepatic glucose production is autoregulated during infusion of gluconeogenic precursors. In hyperglycemic patients with multiple trauma, hepatic glucose production and gluconeogenesis are increased, suggesting that autoregulation of hepatic glucose production may be defective. To better understand the mechanisms of autoregulation and its possible alterations in metabolic stress, lactate was coinfused with glucose in healthy volunteers and in hyperglycemic patients with multiple trauma or critical illness. In healthy volunteers, infusion of glucose alone nearly abolished endogenous glucose production. Lactate increased gluconeogenesis (as indicated by a decrease in net carbohydrate oxidation with no change in total [13C]carbohydrate oxidation) but did not increase endogenous glucose production. In patients with metabolic stress, endogenous glucose production was not suppressed by exogenous glucose, but lactate did not further increase hepatic glucose production. It is concluded that 1) in healthy humans, autoregulation of hepatic glucose production during infusion of lactate is still present when glycogenolysis is suppressed by exogenous glucose and 2) autoregulation of hepatic glucose production is not abolished in hyperglycemic patients with metabolic stress.

An intramedullary alignment guide lodging within the femoral canal during total knee arthroplasty: a case report.

The usual complications of total knee arthroplasty include thrombo-embolism, infection, and loosening. We report an unusual and potentially serious complication of an intramedullary guide lodging within the femoral canal during the procedure. Considering the risk of fracture and additional exposure, the guide was not removed and was cut in situ. The rest of the operation was completed successfully and the patient made an uneventfully recovery.

Body surface area and body weight predict total liver volume in Western adults.

Computed tomography (CT) is used increasingly to measure liver volume in patients undergoing evaluation for transplantation or resection. This study is designed to determine a formula predicting total liver volume (TLV) based on body surface area (BSA) or body weight in Western adults. TLV was measured in 292 patients from four Western centers. Liver volumes were calculated from helical computed tomographic scans obtained for conditions unrelated to the hepatobiliary system. BSA was calculated based on height and weight. Each center used a different established method of three-dimensional volume reconstruction. Using regression analysis, measurements were compared, and formulas correlating BSA or body weight to TLV were established. A linear regression formula to estimate TLV based on BSA was obtained: TLV = -794.41 + 1,267.28 x BSA (square meters; r(2) = 0.46; P <.0001). A formula based on patient weight also was derived: TLV = 191.80 + 18.51 x weight (kilograms; r(2) = 0.49; P <.0001). The newly derived TLV formula based on BSA was compared with previously reported formulas. The application of a formula obtained from healthy Japanese individuals underestimated TLV. Two formulas derived from autopsy data for Western populations were similar to the newly derived BSA formula, with a slight overestimation of TLV. In conclusion, hepatic three-dimensional volume reconstruction based on helical CT predicts TLV based on BSA or body weight. The new formulas derived from this correlation should contribute to the estimation of TLV before liver transplantation or major hepatic resection.

Paralysis of ventilated newborn babies does not influence resistance of the total respiratory system.

Paralysis with pancuronium bromide is used in newborn infants to facilitate ventilatory support during respiratory failure. Changes in lung mechanics have been attributed to paralysis. The aim of this study was to examine whether or not paralysis per se has an influence on the passive respiratory mechanics, resistance (Rrs) and compliance (Crs) of the respiratory system in newborn infants. In 30 infants with acute respiratory failure, Rrs was measured during paralysis with pancuronium bromide and after stopping pancuronium bromide (group A). Rrs was also measured in an additional 10 ventilated infants in a reversed fashion (group B): Rrs was measured first in nonparalysed infants and then they were paralysed, mainly for diagnostic procedures, and the Rrs measurement repeated. As Rrs is highly dependent on lung volume, several parameters, that depend directly on lung volume were recorded: inspiratory oxygen fraction (FI,O2), arterial oxygen tension/alveolar oxygen tension (a/A) ratio and volume above functional residual capacity (FRC). In group A, the Rrs was not different during (0.236+/-0.09 cmH2O x s x mL(-1)) and after (0.237+/-0.07 cmH2O x s x mL(-1)) paralysis. Also, in group B, Rrs did not change (0.207+/-0.046 versus 0.221+/-0.046 cm x s x mL(-1) without versus with pancuronium bromide). FI,O2, a/A ratio and volume above FRC remained constant during paralysis. These data demonstrate that paralysis does not influence the resistance of the total respiratory system in ventilated term and preterm infants when measured at comparable lung volumes.

Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies.

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

Surgical approach for total hip arthroplasty: direct lateral or posterior?

OBJECTIVE: To determine the risks of prosthesis dislocation, postoperative Trendelenburg gait, and sciatic nerve palsy after a posterior approach compared to a direct lateral approach for adult patients undergoing total hip arthroplasty (THA) for primary osteoarthritis (OA). METHODS: Medline, Embase, CINHAL, and Cochrane databases were searched until August 2003. All published trials comparing posterior and direct lateral surgical approaches to THA in adults with a diagnosis of primary hip osteoarthritis were collected. Retrieved articles were assessed independently for their methodological quality. RESULTS: Four prospective cohort studies involving 241 participants met the inclusion criteria. Regarding dislocation rate, no significant difference between posterior and direct lateral surgical approach was found (relative risk 0.35). The presence of postoperative Trendelenburg gait was not significantly different between surgical approaches. The risk of nerve palsy or injury was significantly higher with the direct lateral approach (relative risk 0.16). However, there were no significant differences when comparing this risk nerve by nerve, in particular for the sciatic nerve. Of the other outcomes considered, only the average range of internal rotation in extension of the hip was significantly higher (weighted mean difference 16 degrees ) in the posterior approach group (mean 35 degrees, SD 13 degrees ) compared to the direct lateral approach (mean 19 degrees, SD 13 degrees ). CONCLUSION: The quality and quantity of information extracted from the trials performed to date are insufficient to make a firm conclusion on the optimum choice of surgical approach for adult patients undergoing primary THA for OA.