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PubMed2004

Wear and periprosthetic osteolysis in a match-paired study of modular and nonmodular uncemented acetabular cups.

The wear and prevalence of periprosthetic osteolysis at 5 to 8 years of follow-up of the Trilogy cup, which has a modular liner assembled during surgery, was compared with the Implex cup, which has a fixed liner preassembled at the factory. Sixty-three patients (65 hips) with a Trilogy cup and 64 patients (65 hips) with an Implex cup were match-paired for sex, age, height, weight, and diagnosis (osteoarthritis). All patients had a cemented stem with a 28-mm head and a successful clinical and radiographic result. After an average follow-up of 5.65 years, radiographs were studied to determine the total penetration, using the Livermore technique, and the presence of osteolysis. The average total wear in the Trilogy group was 0.47 mm (range, 0-1.95 mm); for the Implex cup, it was 0.43 mm (range, 0-1.45 mm) (P.99). One patient in each group presented with periacetabular osteolysis (P.99). There was no difference in the wear rate and prevalence of periprosthetic osteolysis between the 2 groups.

Acetabulum↗
PubMed2005

Augments and allografts in revision total knee arthroplasty: usage and outcome using one modular revision prosthesis.

Sixty-five consecutive Coordinate (DePuy, Warsaw, Ind) revision total knee arthroplasties were eligible for minimum 5-year follow-up. Nine patients died and 2 patients were lost. Therefore, 54 knees (51 patients) had a known outcome. Nine knees failed and required either revision or component removal. Eight additional knees were considered clinical failures. Despite the use of metallic augmentation in 89% of the knees, large structural allografts were required in 48% of the knees. Revisions with bone loss that required bulk allograft failed less often (19.2%) than revisions managed without bulk allografts (42.9%). Of 24 knees originally revised for osteolysis/polyethylene wear, only 1 required rerevision for the same mechanism of failure. Modular augments did not effectively address the bone loss and instability encountered in many instances at revision surgery. Survivorship of this implant was 79.4% +/- 13.7% at 8 years.

Adult↗
PubMed2006

Clinical and radiographic assessment of a modular cementless ingrowth femoral stem system for revision hip arthroplasty.

This article presents 6-year mean (2-12-year) clinical and radiographic follow-up of 62 proximally porous-coated modular S-ROM femoral revisions. These patients come from 106 consecutive cases in 97 patients performed by one surgeon between 1987 and 1992 without structural allograft (femoral bone loss was Paprosky types 1-3B). In the 99 cases with known outcome, there were 7 postoperative complications: 2 dislocations (2%), 2 deep infections (2%), 2 periprosthetic femoral fractures (2%), and 1 transient sciatic nerve palsy (1%). There was only 1 revision of the index surgery for a problem related to the stem (dislocation). Of the 62 stems, 59 (95%) with complete follow-up were ingrown, 2 (3%) were loose, and 1 had stable fibrous fixation. This represents a mechanical failure rate of 5%. Stems greater than 16 mm in diameter were more likely to show stress shielding (P = .009) and not to be ingrown (P = .0006).

Adult↗
PubMed2006

Cementless total hip arthroplasty using the modular S-ROM prosthesis combined with corrective proximal femoral osteotomy.

We present the results of total hip arthroplasty using S-ROM (Depuy, Warsaw, Ind) prosthesis combined with corrective femoral transverse osteotomy for hips with proximal femoral deformity. Fourteen hips were followed up for a mean of 61 months (range, 36-95 months), with a mean age at surgery of 55 years (range, 44-69 years). The average intraoperative blood loss was 638 mL, and the average operative time was 136 minutes. The average Harris Hip Score increased from 38.0 (range, 15.0-55.7) preoperatively to 82.0 (range, 34.6-92.7) at the latest follow-up. All the hips except for 1 acquired union of osteotomy and bone ingrowth. S-ROM modular stem, which gives sufficient rotational stability at both proximal and distal parts of the osteotomy, is useful for total hip arthroplasty combined with corrective femoral transverse osteotomy.

Adult↗
PubMed2007

Catastrophic failure of a modular revision total hip polyethylene insert.

Early catastrophic failure of a modular polyethylene component is a potential problem after revision total hip arthroplasty. We describe an unusual case of polyethylene failure that occurred within 18 months of implantation in which no obvious technical error or mechanical failure was identified. The acetabular polyethylene insert was prepared with gas plasma sterilization, and the shelf life was 4 months. Radiographic evaluation used generalized Hough transforms to assess the cup articulation. We identified cup penetration of 2.8 mm before revision and catastrophic destruction of the polyethylene liner at the time of revision. Possible factors implicated for failure included a thin polyethylene liner, increased hip separation, femoral head mismatch, and the high activity level of a younger patient. We believe that this case report highlights the need for future investigations of these subtle factors.

Arthroplasty, Replacement, Hip↗
PubMed2006

Category-specificity can emerge from bottom-up visual characteristics: evidence from a modular neural network.

The role of bottom-up visual processes in category-specific object recognition has been largely unexplored. We examined the role of low-level visual characteristics in category specific recognition using a modular neural network comprising both unsupervised and supervised components. One hundred standardised pictures from ten different categories (five living and five nonliving, including body parts and musical instruments) were presented to a Kohonen self-organising map (SOM) which re-represents the visual stimuli by clustering them within a smaller number of dimensions. The SOM representations were then used to train an attractor network to learn the superordinate category of each item. The ease with which the model acquired the category mappings was investigated with respect to emerging category effects. We found that the superordinates could be separated by very low-level visual factors (as extracted by the SOM). The model also accounted for the well documented atypicality of body parts and musical instrument superordinates. The model has clear relevance to human object recognition since the model was quicker to learn more typical category exemplars and finally the model also accounted for more than 20% of the naming variance in a sample of 57 brain injured subjects. We conclude that purely bottom-up visual characteristics can explain some important features of category-specific phenomena.

Female↗
PubMed2006

Integrated analysis of multiple data sources reveals modular structure of biological networks.

It has been a challenging task to integrate high-throughput data into investigations of the systematic and dynamic organization of biological networks. Here, we presented a simple hierarchical clustering algorithm that goes a long way to achieve this aim. Our method effectively reveals the modular structure of the yeast protein-protein interaction network and distinguishes protein complexes from functional modules by integrating high-throughput protein-protein interaction data with the added subcellular localization and expression profile data. Furthermore, we take advantage of the detected modules to provide a reliably functional context for the uncharacterized components within modules. On the other hand, the integration of various protein-protein association information makes our method robust to false-positives, especially for derived protein complexes. More importantly, this simple method can be extended naturally to other types of data fusion and provides a framework for the study of more comprehensive properties of the biological network and other forms of complex networks.

Algorithms↗
PubMed2005

Design of modular non-viral gene therapy vectors.

Gene delivery has numerous potential applications both clinically and for basic science research. Non-viral vectors represent the long-term future of gene therapy and biomaterials are a critical component for the development of efficient delivery systems. Biomaterial development combined with fundamental studies of virus function and cellular processes will enable the molecular level design of modular vectors. Vectors are being developed based on cationic polymers or lipids that contain functional groups to mediate appropriate interactions with the extracellular environment or to interface with specific cellular processes. This review describes recent progress on the development of biomaterials for non-viral vectors and highlights opportunities for future development. Ultimately, efficient vectors will expand the traditional applications of gene therapy within the clinic and may enable numerous other opportunities within diagnostics, biotechnology, and basic science research.

Biocompatible Materials↗
PubMed2006

Design and modular parallel synthesis of a MCR derived alpha-helix mimetic protein-protein interaction inhibitor scaffold.

A terphenyl alpha-helix mimetic scaffold recognized to be capable of disrupting protein-protein interactions was structurally morphed into an easily amenable and versatile multicomponent reaction (MCR) backbone. The design, modular in-parallel library synthesis, initial cell based biological data, and preliminary in vitro screening for the disruption of the Bcl-w/Bak protein-protein interaction by representatives of the MCR derived scaffold are presented.

Apoptosis↗
PubMed2004

Modular synthesis and preliminary biological evaluation of stereochemically diverse 1,3-dioxanes.

Modular synthesis and substrate stereocontrol were combined to furnish 18,000 diverse 1,3-dioxanes whose distribution in chemical space rivals that of a reference set of over 2,000 bioactive small molecules. Library quality was assessed at key synthetic stages, culminating in a detailed postsynthesis analysis of purity, yield, and structural characterizability, and the resynthesis of library subsets that did not meet quality standards. The importance of this analysis-resynthesis process is highlighted by the discovery of new biological probes through organismal and protein binding assays, and by determination of the building block and stereochemical basis for their bioactivity. This evaluation of a portion of the 1,3-dioxane library suggests that many additional probes for chemical genetics will be identified as the entire library becomes biologically annotated.

Amines↗
PubMed2004

bryA: an unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina.

"Candidatus Endobugula sertula," the uncultivated bacterial symbiont of Bugula neritina, is the proposed source of the bryostatin family of anticancer compounds. We cloned a large modular polyketide synthase (PKS) gene complex from "Candidatus Endobugula sertula" and characterized one gene, bryA, which we propose is responsible for the initial steps of bryostatin biosynthesis. Typical PKS domains are present. However, acyltransferase domains are lacking in bryA, and beta-ketoacyl synthase domains of bryA cluster with those of PKSs with discrete, rather than integral, acyltransferases. We propose a model for biosynthesis of the bryostatin D-lactate starter unit by the bryA loading module, utilizing atypical domains homologous to FkbH, KR, and DH. The bryA gene product is proposed to synthesize a portion of the pharmacologically active part of bryostatin and may be useful in semisynthesis of clinically useful bryostatin analogs.

Amino Acid Sequence↗
PubMed2005

Molecular basis of Celmer's rules: stereochemistry of catalysis by isolated ketoreductase domains from modular polyketide synthases.

A system is reported for the recombinant expression of individual ketoreductase (KR) domains from modular polyketide synthases (PKSs) and scrutiny of their intrinsic specificity and stereospecificity toward surrogate diketide substrates. The eryKR(1) and the tylKR(1) domains, derived from the first extension module of the erythromycin PKS and the tylosin PKS, respectively, both catalyzed reduction of (2R, S)-2-methyl-3-oxopentanoic acid N-acetylcysteamine thioester, with complete stereoselectivity and stereospecificity, even though the substrate is not tethered to an acyl carrier protein or an intact PKS multienzyme. In contrast, and to varying degrees, the isolated enzymes eryKR(2), eryKR(5), and eryKR(6) exercised poorer control over substrate selection and the stereochemical course of ketoreduction. These data, together with modeling of diketide binding to KR(1) and KR(2), demonstrate the fine energetic balance between alternative modes of presentation of ketoacylthioester substrates to KR active sites.

Binding Sites↗
PubMed2005

Analytical performance and workflow evaluation of the Roche E170 modular immunoassay analyzer in a pediatric setting.

OBJECTIVES: To evaluate the analytical performance of the Roche E170 modular analytics immunoassay analyzer and assess its impact on workflow efficiency and ability to consolidate workstations in a pediatric setting. DESIGN AND METHODS: Analytical performance of eleven common immunoassays was assessed. Total imprecision was determined using Roche PreciControl Universal controls, Bio-Rad Lyphochek Immuno Plus, Anemia controls, and a human serum pool. Method comparison was performed with approximately 100 patient specimens. High dose hook effect, sample carryover, and results comparison between the two measuring channels were evaluated. For the workflow study, the time required for sample and reagent handling, instrument preparation, and hands-on time were assessed. RESULTS: Correlation coefficients with existing methods ranged from 0.941 to 0.999. Biases of -19% to 70% were observed. Total imprecision ranged from 1.1 to 7.6%. No sample carryovers were encountered. Results from both measuring channels were comparable. CONCLUSION: E170 is suitable for use in a pediatric setting. The analytical performance is acceptable and gives equivalent results to our existing systems. The precision is comparable and acceptable. Some improvement in efficiency, workflow, cost saving, and consolidation of workstations is possible. Significant workflow improvements can only be realized when integrated with the chemistry modules.

Autoanalysis↗
PubMed2004

Endovascular grafting of complex aortic aneurysms with a modular side branch stent-graft system in a porcine model.

OBJECTIVES: To evaluate and refine a stent-graft system with side branches for treatment of aneurysms with essential branch arteries. METHODS: In a porcine model (n=4) supra- and juxta-renal aortic aneurysms were created by suturing an artificial patch onto an anterior aortotomy. Angiography was performed to determine the exact location of the renal arteries. Accordingly, fenestrations were created in an appropriately sized aortic stent-graft. Initial deployment of the aortic graft is partial, whereby the top stent is secured in a cap and distal stents are being restrained, thus ensuring longitudinal and rotational manoeuvrability during alignment of the branch arteries. Separate branch grafts with silicone flanges for connection with the main stent-graft are subsequently placed in the renal arteries followed by full deployment of the main stent-graft. Outcome was evaluated by postoperative angiography and autopsy results and by measuring operating time, blood loss and use of contrast agent. RESULTS: Branched grafts were placed successfully in all trials. The median endovascular procedure time was 126 min (90-160), with 575 ml (400-800) blood loss and 65 ml (50-80) contrast agent use. Angiographically, all aneurysms were excluded without signs of endoleak and all renal arteries were patent. At autopsy, the main stent-graft and all side branches were adequately placed with intact connections between main stent-graft and branch grafts. CONCLUSIONS: In this model, endovascular repair of complex aneurysms using a modular branch graft system is feasible in a reliable, predictable and timely fashion.

Animals↗
PubMed2005

Modular training for residents with no prior experience with open pelvic surgery in endoscopic extraperitoneal radical prostatectomy.

PURPOSE: To establish a teaching program for the performance of endoscopic extraperitoneal radical prostatectomy (EERPE) that would ascertain the safe and efficacious training of residents with no previous experience with open pelvic surgery. MATERIALS AND METHODS: The technique of EERPE was divided in 12 segments with 5 levels of difficulty. We thus designed a training program, where the resident learned the procedure in a mentor-defined schedule. During each educational EERPE, the trainee only performed the operative steps corresponding to his acquired skill level. The mentor performed the remaining parts of the EERPE, with the trainee assisting. The first 50 and consequent 100 cases performed by the residents were compared to the first 50 and last 100 cases (cases 521-621) performed by the mentor. RESULTS: Two residents with no prior experience with open pelvic surgery participated in the study, and required 43 and 38 procedures respectively, until they were considered to be competent. The initial 50 procedures performed completely independently by the residents had mean operative times of 176 and 173 minutes. There were 2 intraoperative rectal injuries (one patient developed recto-urethral fistula), and 1 hemorrhage, and 1 lymphocele, postoperatively. The positive margin rate for pT2 disease was 14.3 and 11.5%, and for pT3 tumors 38.8 and 29.1%, respectively. After an additional 100 procedures operated by the same residents, mean operative times were 142 and 146 minutes. There was one patient who needed a transfusion. Postoperative complications requiring re-intervention were 1 hemorrhage, 2 anastomotic leakages and 4 symptomatic lymphoceles. The positive margin rate for pT2 disease was 12.8% and 6.5%, and for pT3 tumors 33.3% and 26.3% respectively. No statistical significant differences were observed when comparing with the mentors cases. CONCLUSION: We have showed that residents with no prior experience in open surgery of the pelvis can adhere to the modular training scheme and successfully perform the EERPE procedure with similar risk of complications compared to the tutor.

Clinical Competence↗
PubMed2004

Rhamnogalacturonan lyase reveals a unique three-domain modular structure for polysaccharide lyase family 4.

Rhamnogalacturonan lyase (RG-lyase) specifically recognizes and cleaves alpha-1,4 glycosidic bonds between L-rhamnose and D-galacturonic acids in the backbone of rhamnogalacturonan-I, a major component of the plant cell wall polysaccharide, pectin. The three-dimensional structure of RG-lyase from Aspergillus aculeatus has been determined to 1.5 A resolution representing the first known structure from polysaccharide lyase family 4 and of an enzyme with this catalytic specificity. The 508-amino acid polypeptide displays a unique arrangement of three distinct modular domains. Each domain shows structural homology to non-catalytic domains from other carbohydrate active enzymes.

Amino Acid Sequence↗
PubMed2005

Activation of the transcription factor NFAT1: concerted or modular regulation?

The transcription factor NFAT1 is activated through dephosphorylation of multiple serine residues, contained within the SRR1 and SP motifs. The phosphorylation status of these motifs regulates the subcellular localisation of NFAT1 via a conformational switch. Here, we discuss two molecular mechanisms for NFAT1 activation that resemble network-oriented approaches. In the modular mechanism, import and export are regulated separately by the SRR1 and SP motifs, respectively, whereas in the concerted model all residues jointly control both processes. Using simulations of a computational model, we show that both mechanisms may be compatible with recent experimental data on the import and export kinetics of NFAT1.

DNA-Binding Proteins↗