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A new modular chemiluminescence immunoassay analyser evaluated.

Thyrotropin (TSH), free thyroxine (fT4) and testosterone assays have been used as a probe to evaluate the performances of a new modular chemiluminescence (CL) immunoassay analyser, the Abbott Architect 2000. The evaluation was run in parallel on other systems that use CL as the detection reaction: DPC Immulite, Chiron Diagnostics ACS-180 and ACS Centaur (TSH functional sensitivity only). TSH functional sensitivity was 0.0012, 0.009, 0.033 and 0.039 mU/I for the Architect, Immulite, ACS Centaur and ACS-180, respectively. Testosterone functional sensitivity was 0.38, 3.7 and 2.0 nmol/l for Architect, Immulite and ACS-180, respectively. Good correlation was obtained between the ACS-180 and Architect for all assays. The Immulite correlation did not agree well with the Architect or ACS-180 for fT4 and testosterone but was in good agreement for TSH. Regarding fT4 and testosterone, equilibrium dialysis and isotopic dilution gas-chromatography mass-spectrometry (GC-MS) respectively were used as reference methods. For both within- and between-run precision, the Architect showed the best reproducibility for all three analytes (CV < 6%).

Automation↗

Modular propagation of epileptiform activity: evidence for an inhibitory veto in neocortex.

What regulates the spread of activity through cortical circuits? We present here data indicating a pivotal role for a vetoing inhibition restraining modules of pyramidal neurons. We combined fast calcium imaging of network activity with whole-cell recordings to examine epileptiform propagation in mouse neocortical slices. Epileptiform activity was induced by washing Mg2+ ions out of the slice. Pyramidal cells receive barrages of inhibitory inputs in advance of the epileptiform wave. The inhibitory barrages are effectively nullified at low doses of picrotoxin (2.5-5 microM). When present, however, these inhibitory barrages occlude an intense excitatory synaptic drive that would normally exceed action potential threshold by approximately a factor of 10. Despite this level of excitation, the inhibitory barrages suppress firing, thereby limiting further neuronal recruitment to the ictal event. Pyramidal neurons are recruited to the epileptiform event once the inhibitory restraint fails and are recruited in spatially clustered populations (150-250 microm diameter). The recruitment of the cells within a given module is virtually simultaneous, and thus epileptiform events progress in intermittent (0.5-1 Hz) steps across the cortical network. We propose that the interneurons that supply the vetoing inhibition define these modular circuit territories.

Action Potentials↗

Functional magnetic resonance imaging examination of two modular architectures for switching multiple internal models.

An internal model is a neural mechanism that can mimic the input-output properties of a controlled object such as a tool. Recent research interests have moved on to how multiple internal models are learned and switched under a given context of behavior. Two representative computational models for task switching propose distinct neural mechanisms, thus predicting different brain activity patterns in the switching of internal models. In one model, called the mixture-of-experts architecture, switching is commanded by a single executive called a "gating network," which is different from the internal models. In the other model, called the MOSAIC (MOdular Selection And Identification for Control), the internal models themselves play crucial roles in switching. Consequently, the mixture-of-experts model predicts that neural activities related to switching and internal models can be temporally and spatially segregated, whereas the MOSAIC model predicts that they are closely intermingled. Here, we directly examined the two predictions by analyzing functional magnetic resonance imaging activities during the switching of one common tool (an ordinary computer mouse) and two novel tools: a rotated mouse, the cursor of which appears in a rotated position, and a velocity mouse, the cursor velocity of which is proportional to the mouse position. The switching and internal model activities temporally and spatially overlapped each other in the cerebellum and in the parietal cortex, whereas the overlap was very small in the frontal cortex. These results suggest that switching mechanisms in the frontal cortex can be explained by the mixture-of-experts architecture, whereas those in the cerebellum and the parietal cortex are explained by the MOSAIC model.

Adult↗

Structure-based kinetic models of modular signaling protein function: focus on Shp2.

We present here a computational, rule-based model to study the function of the SH2 domain-containing protein tyrosine phosphatase, Shp2, in intracellular signal transduction. The two SH2 domains of Shp2 differentially regulate the enzymatic activity by a well-characterized mechanism, but they also affect the targeting of Shp2 to signaling receptors in cells. Our kinetic model integrates these potentially competing effects by considering the intra- and intermolecular interactions of the Shp2 SH2 domains and catalytic site as well as the effect of Shp2 phosphorylation. Even for the isolated Shp2/receptor system, which may seem simple by certain standards, we find that the network of possible binding and phosphorylation states is composed of over 1000 members. To our knowledge, this is the first kinetic model to fully consider the modular, multifunctional structure of a signaling protein, and the computational approach should be generally applicable to other complex intermolecular interactions.

Computer Simulation↗

Three-year experience with modular stent-graft devices for endovascular AAA treatment.

PURPOSE: To evaluate feasibility and present early results of endovascular abdominal aortic aneurysm (AAA) exclusion using modular stent-grafts. METHODS: In a 3-year period ending July 1997, 201 patients were treated with self-expanding stent-grafts for AAAs with infrarenal necks > or = 10 to 15 mm long and < or = 32 mm wide; subtotal mural thrombus, calcification, and even angulation to some extent were acceptable, as were iliac arteries up to 18 mm wide. The patients were treated with either the Stentor/Vanguard device (178 cases) or the Talent endograft (23 cases). Follow-up on all patients was conducted at 3, 6, 12, 18, and 24 months. RESULTS: The technical aneurysm exclusion rate was 89% (178/201). There were 18 primary endoleaks (9.0%; 2 proximal, 16 distal), 4 (2.0%) conversions to open surgery, and 1 (0.5%) failure to deploy the graft. Seven (3.5%) patients died in the perioperative period, 5 due to multiorgan failure early in the series and two of hemorrhagic complications. Five (2.5%) renal artery occlusions were encountered; in one case, the graft was removed after 3 weeks. Nineteen late endoleaks were found in follow-up, related primarily to the iliac limb graft extensions of the Stentor device, graft material problems, or unknown causes. To date, 10 primary and 13 secondary endoleaks have been treated endovascularly. Twenty (10.0%) graft-limb thromboses were treated either by thrombolysis, thrombectomy, or a femorofemoral bypass. CONCLUSIONS: Endovascular grafting is technically feasible and becomes easier with improvements of the introducer systems and the grafts. The seemingly high complication rate in this series is due to the liberal patient selection criteria.

Aged↗

Time-related alterations in shape, position, and structure of self-expanding, modular aortic stent-grafts: a 4-year single-center follow-up.

PURPOSE: To report the nature and ramifications of structural and positional changes over time in tube and modular bifurcated aortic stent-grafts. METHODS: Two hundred ninety-one patients received endovascular aortic grafts (primarily Stentor/Vanguard) between August 1994 and August 1998. Follow-up surveillance (clinical and laboratory examination, biplanar noncontrast radiography, and contrast-enhanced computed tomography) has been maintained on all patients for 4 years. Changes in the configuration and position of endografts have been noted and their sequelae charted. RESULTS: Three types of endograft shape changes have been documented: mild -- slight distortions visible on plain radiographs (n = 90, 31.0%), significant -- angulations reaching 60 degrees to 90 degrees (n = 65, 22.3%), and severe -- angulations > or = 90 degrees (n = 10, 3.4%). Changes in position never gave rise to late migration at the proximal attachment site, whereas at the distal ends, the endograft easily retracted from the iliac arteries (n = 8). Structural alterations (rupture of the stent frame, sutures, or fabric, and total graft disintegration) were more common in the original Stentor model. Shape, position, and structural alterations were mutually dependent and led to secondary endoleaks (n = 26) and graft limb thrombosis (n = 37). Late surgical conversion was necessary in 3 (1.0%) patients. CONCLUSIONS: Tortuosity of the native vessels is a source of complication in long-term follow-up just as it is during implantation. Given the late appearance of complications in this patient cohort, it would seem that the durability of an endograft cannot be evaluated with < 3 years of follow-up.

Aged↗

The use of a modular titanium endoprosthesis in skeletal reconstructions after bone tumor resections: method presentation and analysis of 37 cases.

We analyzed 37 patients who underwent segmental wide resection of bone tumors and reconstruction with a modular titanium endoprosthesis at the Orthopaedic Oncology Group, between 1992 and 1998. Twelve patients were male and 25 were female, with a mean age of 30 years (9 - 81). The mean follow-up was 14 months (2 - 48). The diagnoses were: osteosarcoma (14 cases), metastatic carcinoma (10), Ewing's sarcoma (4), giant cell tumor (4), malignant fibrous histiocytoma (3), chondrosarcoma (1), and aneurysmal bone cyst (1). Eleven articulated total knee, 8 partial proximal femur with bipolar acetabulum, 8 partial proximal humerus, 3 total femur, 2 partial proximal tibia, 2 diaphyseal femur, 2 diaphyseal humerus, and 1 total proximal femur with cementless acetabulum endoprosthesis implant procedures were done. The complications related to the procedure included: infection (5 cases), dislocation (3), module loosening (1), and ulnar nerve paresthesia (1). We used the following criteria for the clinical evaluation: presence of pain, range of motion, reconstruction stability, surgical and oncologic complications, and patient acceptance. The results were good in 56.8% of the cases, regular in 32.4% and poor in 10.8%.

Adolescent↗

Carrier phase shifted SPWM based on current sourced multi-modular converter for active power filter.

A novel current-source active power filter (APF) based on multi-modular converter with carrier phase-shifted SPWM (CPS-SPWM) technique is proposed. With this technique, the effect of equivalent high switching frequency converter is obtained with low switching frequency converter. It is very promising in current-source APF that adopt superconducting magnetic energy storage component.

Computer-Aided Design↗

Rapid generation of stable transgenic embryonic stem cell lines using modular lentivectors.

Generation of stable transgenic embryonic stem (ES) cell lines by classic transfection is still a difficult task, requiring time-consuming clonal selection, and hampered by clonal artifacts and gene silencing. Here we describe a novel system that allows construction of lentivectors and generation of stable ES cell lines with > 99% transgene expression within a very short time frame. Rapid insertion of promoters and genes of interest is obtained through a modular recombinational cloning system. Vectors contain central polypurine tract from HIV-1 element and woodchuck hepatitis virus post-transcriptional regulatory element as well as antibiotic resistance to achieve optimal and homogenous transgene expression. We show that the system 1) is functional in mouse and human ES cells, 2) allows the generation of ES cells expressing genes of interest under the control of ubiquitous or tissue-specific promoters, and 3) allows ES cells expressing two constructs through selection with different antibiotics to be obtained. The technology described herein should become a useful tool in stem cell research.

Animals↗

Clinical results of modular polyethylene insert exchange with retention of total knee arthroplasty components.

BACKGROUND: Modular polyethylene inserts have enabled surgeons to perform an isolated tibial insert exchange while retaining well fixed components. The purpose of this study was to review the results of insert revision and to clarify the role of this option compared with that of revision total knee arthroplasty. METHODS: Fifty-six patients (sixty-three knees) were managed with revision of a tibial polyethylene insert and retention of well aligned and stable femoral and tibial components. The implants had been in situ for an average of fifty-nine months (range, two to 108 months) at the time of the insert exchange. The inserts that were removed at the time of exchange were evaluated with regard to wear of the articular surface according to the classification system of Hood et al. and with regard to undersurface wear according to the method described by Wasielewski et al. Forty-eight knees were followed for an average of 7.4 years (range, 3.0 to 12.2 years) after the insert exchange. Knees that did not require an additional operation were considered to have had a successful exchange. RESULTS: Seven of the forty-eight exchanges failed, at an average of fifty-four months, because of accelerated wear of the new insert. All seven knees required complete revision of all components. Of the twenty-two exchanges that were performed because of severe wear of the primary insert, six (27 percent) failed at an average of less than five years; thus, knees in which the exchange was performed because of advanced wear were more likely to fail again (p < 0.05). In addition, primary inserts that were removed from knees in which the exchange procedure subsequently failed had higher delamination scores than those that were removed from knees in which the exchange was successful (p < 0.05). Most of the primary inserts had substantial undersurface wear at the time of the exchange procedure. Metallosis (thirty knees) and osteolysis (nineteen knees) were unrelated to failure of the exchange. CONCLUSIONS: An isolated revision of the tibial polyethylene insert should not be performed when there is accelerated wear of the insert with severe delamination and grade-3 or 4 undersurface wear within ten years after the primary procedure. Because a variety of patient-related, implant-related, and technical factors influence polyethylene wear, the orthopaedist must consider multiple variables whenever contemplating a limited revision.

Arthroplasty, Replacement, Knee↗

The press-fit condylar modular total knee system with a posterior cruciate-substituting design. A concise follow-up of a previous report.

The purpose of the present study was to determine the long-term results of a series of 150 consecutive primary posterior stabilized modular knee arthroplasties that had been performed in 118 patients with use of a circumferential tibial insert capture as described in a previous report, published in 1997. The patients were evaluated with use of a patient-administered questionnaire; Knee Society clinical, functional, and radiographic scoring systems; and Kaplan-Meier survivorship analysis. A good to excellent result was confirmed in seventy-six (90%) of the eighty-four patients (105 knees) with a mean duration of follow-up of twelve years (range, ten to thirteen years). At twelve years, the survival rate was 94.6% +/- 4.0% with failure for any reason as the end point and 98.3% +/- 2.4% with mechanical failure as the end point. Revision surgery was performed in five knees because of infection (two knees), dislocation (one knee), and substantial polyethylene wear with femoral osteolysis (two knees). We concluded that, while fixation failure is rare, polyethylene wear and osteolysis are emerging as important causes of failure.

Arthroplasty, Replacement, Knee↗

A modular theory of autoimmunity.

The traditional overarching concept of disease pathogenesis entails the natural history of disease, i.e. the concept that any disease is a unified entity from beginning to termination. The concept of the natural history of disease encourages researchers and clinicians alike to conceptualize all clinical signs and symptoms in a patient as manifestations of a single disease process. Our experiences in dissecting the genetic control of autoimmune diseases and autoimmune phenotypes suggest that for many autoimmune processes, an alternative conceptual framework may be more useful. We term this approach a "modular" theory of autoimmunity. "Modules" are distinct, genetically controlled clinical or pathological phenotypes which can interact to construct a disease process. Modules may interact additively, synergistically, or antagonistically in any given individual. Multiple modules can coexist and produce unique disease phenotypes. We illustrate this concept with examples from the murine autoimmune model of type one diabetes, the nonobese diabetic (NOD) mouse.

Animals↗

Modular kinetic analysis of the adenine nucleotide translocator-mediated effects of palmitoyl-CoA on the oxidative phosphorylation in isolated rat liver mitochondria.

To test whether long-chain fatty acyl-CoA esters link obesity with type 2 diabetes through inhibition of the mitochondrial adenine nucleotide translocator, we applied a system-biology approach, dual modular kinetic analysis, with mitochondrial membrane potential (Deltapsi) and the fraction of matrix ATP as intermediates. We found that 5 mumol/l palmitoyl-CoA inhibited adenine nucleotide translocator, without direct effect on other components of oxidative phosphorylation. Indirect effects depended on how oxidative phosphorylation was regulated. When the electron donor and phosphate acceptor were in excess, and the mitochondrial "work" flux was allowed to vary, palmitoyl-CoA decreased phosphorylation flux by 38% and the fraction of ATP in the medium by 39%. Deltapsi increased by 15 mV, and the fraction of matrix ATP increased by 46%. Palmitoyl-CoA had a stronger effect when the flux through the mitochondrial electron transfer chain was maintained constant: Deltapsi increased by 27 mV, and the fraction of matrix ATP increased 2.6 times. When oxidative phosphorylation flux was kept constant by adjusting the rate using hexokinase, Deltapsi and the fraction of ATP were not affected. Palmitoyl-CoA increased the extramitochondrial AMP concentration significantly. The effects of palmitoyl-CoA in our model system support the proposed mechanism linking obesity and type 2 diabetes through an effect on adenine nucleotide translocator.

Animals↗

Modular seating for paralytic scoliosis: design and initial experience.

The conventional wheelchair sling seat provides little or no support to the spine of a child with myopathy or neurogenic muscular weakness. As the spinal muscles become weaker scoliosis may develop with associated deformity, pain and restriction of cardio-respiratory function. If muscle weakness is severe, the resultant fully developed deformity is virtually impossible to treat. Slowing the rate of increase of the deformity is, therefore, the most hopeful avenue of attack. This work addresses the hypothesis that custom moulded seating can increase sitting comfort and slow the rate of progression of spinal curvature in children with paralytic scoliosis, and further, that a range of standard or modular seats can achieve these goals at less cost. Previous work on this problem has ranged from simply padding the armrest, in order to distribute force over the rib cage, through to custom moulded seating. Our initial experience with custom moulding, using the bean bag evacuation and consolidation technique, produced several comfortable seats although the technique was labour intensive and therefore costly. This led us to attempt to develop a method of providing comfortable seating that would help control spinal deformity at reasonable cost. This paper describes the design of a standardized seating system for school age children with myopathy or neurogenic muscular weakness. Preliminary results indicate that this technique may have advantages over alternative methods of treatment. The radiological study is continuing.

Child↗

Development and testing of thermoplastic structural components for modular prostheses.

The wider use of thermoplastic structural components in modular artificial limbs would enable their general properties of low density, corrosion resistance and mouldability and more specific properties of certain thermoplastics such as shock absorption, fatigue and wear resistance to be used to the advantage of patients and manufacturers. They provide an alternative to metal and carbon fibre reinforced resin systems. Emphasis has been placed on the development of rotationally moulded Nylon 11 shank sections, using Philadelphia recommended load levels as the design criteria for structural integrity. Laboratory testing underlined the importance of fatigue testing of thermoplastic components since structural deterioration due to creep--a time dependent mechanical property of thermoplastics--can be ascertained in fatigue testing but would not be evident on the shorter timescale of the static test. Experimental below-knee prostheses incorporating suitably designed plastic shanks and alignment devices can withstand high static loads and exhibit long fatigue lifetimes in excess of 2 million cycles. The shank design offered an opportunity for testing under service conditions the validity of the Philadelphia Static Load level (2.5 kN) since shank failure loads are around this figure. Patient trials of experimental prostheses based on various combinations of plastic shanks and alignment devices and conducted over 33 months indicate that the Static Load Level along with fatigue testing is a satisfactory test criterion for general service use of thermoplastic prosthetic components.

Artificial Limbs↗

Lightweight modular orthosis.

Background and highlights are presented concerning the development of a new orthotic system judged to be "the most outstanding innovation in prosthetics and/or orthotics practice" during the 1986-1989 period. The first Brian Blatchford Prize was awarded at the Sixth World Congress of ISPO held in Kobe, Japan. November 12-17, 1989. The new development selected as most deserving of this award consists of a system utilizing inexpensive, lightweight, modular components which can be quickly assembled with a few hand tools to provide custom-fitted knee-ankle-foot orthoses for persons with paraplegia and quadriplegia. These leg frames support standing and permit the patient to begin receiving the physical and psychological benefits of weightbearing as soon as medically feasible after injury. Later, if desired, specially designed knee-joints, with a variety of possible locking features, can be installed on the existing leg frames at a reasonable cost.

Braces↗

A new modular six-bar linkage trans-femoral prosthesis for walking and squatting.

Four-bar linkage mechanisms produced by many designers of knee joints for trans-femoral prostheses can provide knee rotation to permit walking only. In Afro-Asian countries people are accustomed to a squatting posture in their daily activities. A six-bar linkage knee-ankle mechanism trans-femoral prosthesis is described which was developed and fitted to an amputee. The motion patterns of the ankle, knee and thigh during walking and squatting (obtained using a flickering light emitting diode system) for the above prosthesis is compared with motion patterns obtained for normal subjects. The closeness between both the patterns establishes the suitability of the new modular trans-femoral prosthesis for producing near normal patterns of motion during walking and squatting. The additional facility of cross-legged sitting provided in the prosthesis makes it functionally suitable for Afro-Asian amputees.

Amputees↗

Late disassembly of modular acetabular components. A report of two cases.

We report two cases of late disassembly of modular acetabular components, 4 and 5 years after implantation. One was revised immediately after the disassembly and one after 4 months, the latter demonstrating excessive wear of metal and polyethylene. Radiographs showing eccentric displacement of the femoral head in the cup associated with a dark, curved shadow representing the displaced polyethylene insert identify this type of implant failure.

Aged↗