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Biomedical subjects

J M Hollis

Publications and source records attributed to J M Hollis.

At least 19 recordsLinked to original sources

The relationships between instrumented measurements of ankle and knee ligamentous laxity and generalized joint laxity.

AIM: The purpose of this study was to evaluate whether lower extremity joint laxity is a function of a particular joint and/or a generalizable characteristic (trait) of the person. Validated instrumented measurements of ankle and knee joint-specific laxity in the same individual were correlated to determine whether a relationship exists. In addition, ankle and knee joint-specific laxity were correlated with generalized joint laxity using the modified Beighton mobility index. METHODS: Fifty-seven male and female athletes were studied. We examined dominant ankle laxity using an ankle arthrometer and dominate knee anterior laxity using the KT 2000. The dominant ankle was loaded in anteroposterior (AP) drawer and inversion-eversion (I-E) rotation. Laxity was measured as total AP displacement (millimeters) after +/-125 N of applied force and total I-E rotation (degrees) was measured after +/-4 N x m of applied torque. The dominant knee was loaded with an anterior drawer and laxity (millimeters) was measured after manual maximum displacement. RESULTS: Non-significant correlations were observed among the test variables for generalized joint laxity (0.21 to 0.37; P>0.05) and instrumented ankle and knee joint laxity (0.19 to 0.21; P>0.05). When examined by gender, no statistically significant correlations (0.05 to 0.40; P>0.05) were found for either generalized laxity or instrumented ankle and knee joint laxity. CONCLUSIONS: These results imply that ankle and knee joint laxity are joint-specific and not generalizable.

Adult↗

Using a linked soil model emulator and unsaturated zone leaching model to account for preferential flow when assessing the spatially distributed risk of pesticide leaching to groundwater in England and Wales.

Although macropore flow is recognized as an important process for the transport of pesticides through a wide range of soils, none of the existing spatially distributed methods for assessing the risk of pesticide leaching to groundwater account for this phenomenon. The present paper presents a spatially distributed modelling system for predicting pesticide losses to groundwater through micro- and macropore flow paths. The system combines a meta version of the mechanistic, dual porosity, preferential flow pesticide leaching model MACRO (the MACRO emulator), which describes pesticide transport and attenuation in the soil zone, to an attenuation factor leaching model for the unsaturated zone. The development of the emulator was based on the results of over 4000 MACRO model simulations. Model runs describe pesticide leaching for the range of soil types, climate regimes, pesticide properties and application patterns in England and Wales. Linking the MACRO emulator to existing spatial databases of soil, climate and compound-specific loads allowed the prediction of the concentration of pesticide leaching from the base of the soil profile (at 1 m depth) for a wide range of pesticides. Attenuation and retardation of the pesticide during transit through the unsaturated zone to the watertable was simulated using the substrate attenuation factor model AQUAT. The MACRO emulator simulated pesticide loss in 10 of 12 lysimeter soil-pesticide combinations, for which pesticide leaching was shown to occur and also successfully predicted no loss from 3 soil-pesticide combinations. Although the qualitative aspect of leaching was satisfactorily predicted, actual pesticide concentrations in leachate were relatively poorly predicted. At the national scale, the linked MACRO emulator/AQUAT system was found to predict the relative order of, and realistic regional patterns of, pesticide leaching for atrazine, isoproturon, chlorotoluron and lindane. The methodology provides a first-step assessment of the potential for pesticide leaching to groundwater in England and Wales. Further research is required to improve the modelling concept proposed. The system can be used to refine regional groundwater monitoring system designs and sampling strategies and improve the cost-effectiveness of the measures needed to achieve 'good status' of groundwater quality as required by the Water Framework Directive.

Journal Article↗

The strength of a cement acetabular locking mechanism.

To minimize the morbidity associated with revision of a well-fixed acetabular shell, some surgeons advocate cementing a polyethylene liner into the shell when a liner exchange is not possible. So far the strength of this cement locking mechanism has been measured on only a few specimens. The purpose of this study is to correct that oversight by measuring the push-out and lever-out strengths of an acetabular polyethylene liner cemented into a porous-coated shell. We cemented acetabular liners into porous-coated acetabular shells using first-generation cementing techniques. Each of 30 specimens was tested for its push-out or lever-out strength. The results suggest that the strength of a cemented polyethylene liner locking mechanism is similar to that of an uncemented acetabular shell.

Acetabulum↗

Aspartyl beta -hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin.

The mouse aspartyl beta-hydroxylase gene (Asph, BAH) has been cloned and characterized. The mouse BAH gene spans 200 kilobase pairs of genomic DNA and contains 24 exons. Of three major BAH-related transcripts, the two largest (6,629 and 4,419 base pairs) encode full-length protein and differ only in the use of alternative polyadenylation signals. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila. Monoclonal antibody reagents were generated, epitope-mapped, and used to definitively correlate RNA bands on Northern blots with protein species on Western blots. The gene for mouse junctin, a calsequestrin-binding protein, was cloned and characterized and shown to be encoded from the same locus. When expressed in heart tissue, BAH/humbug preferably use the first exon and often the fourth exon of junctin while preserving the reading frame. Thus, three individual genes share common exons and open reading frames and use separate promoters to achieve differential expression, splicing, and function in a variety of tissues. This unusual form of exon sharing suggests that the functions of junctin, BAH, and humbug may be linked.

Amino Acid Sequence↗

Pesticides in rainfall in Europe.

Papers and published reports investigating the presence of pesticides in rainfall in Europe were reviewed. Approximately half of the compounds that were analysed for were detected. For those detected, most concentrations were below about 100 ng/l, but larger concentrations, up to a few thousand nanograms per litre, were detected occasionally at most monitoring sites. The most frequently detected compounds were lindane (gamma-HCH) and its isomer (alpha-HCH), which were detected on 90-100% of sampling occasions at most of the sites where they were monitored. For compounds developed more recently, detection was usually limited to the spraying season. A classification of pesticides according to their deposition pattern is proposed.

Journal Article↗

Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine.

Dexfenfluramine was approved in the United States for long-term use as an appetite suppressant until it was reported to be associated with valvular heart disease. The valvular changes (myofibroblast proliferation) are histopathologically indistinguishable from those observed in carcinoid disease or after long-term exposure to 5-hydroxytryptamine (5-HT)(2)-preferring ergot drugs (ergotamine, methysergide). 5-HT(2) receptor stimulation is known to cause fibroblast mitogenesis, which could contribute to this lesion. To elucidate the mechanism of "fen-phen"-associated valvular lesions, we examined the interaction of fenfluramine and its metabolite norfenfluramine with 5-HT(2) receptor subtypes and examined the expression of these receptors in human and porcine heart valves. Fenfluramine binds weakly to 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors. In contrast, norfenfluramine exhibited high affinity for 5-HT(2B) and 5-HT(2C) receptors and more moderate affinity for 5-HT(2A) receptors. In cells expressing recombinant 5-HT(2B) receptors, norfenfluramine potently stimulated the hydrolysis of inositol phosphates, increased intracellular Ca(2+), and activated the mitogen-activated protein kinase cascade, the latter of which has been linked to mitogenic actions of the 5-HT(2B) receptor. The level of 5-HT(2B) and 5-HT(2A) receptor transcripts in heart valves was at least 300-fold higher than the levels of 5-HT(2C) receptor transcript, which were barely detectable. We propose that preferential stimulation of valvular 5-HT(2B) receptors by norfenfluramine, ergot drugs, or 5-HT released from carcinoid tumors (with or without accompanying 5-HT(2A) receptor activation) may contribute to valvular fibroplasia in humans.

Animals↗

Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family.

Aggrecan is responsible for the mechanical properties of cartilage. One of the earliest changes observed in arthritis is the depletion of cartilage aggrecan due to increased proteolytic cleavage within the interglobular domain. Two major sites of cleavage have been identified in this region at Asn(341)-Phe(342) and Glu(373)-Ala(374). While several matrix metalloproteinases have been shown to cleave at Asn(341)-Phe(342), an as yet unidentified protein termed "aggrecanase" is responsible for cleavage at Glu(373)-Ala(374) and is hypothesized to play a pivotal role in cartilage damage. We have identified and cloned a novel disintegrin metalloproteinase with thrombospondin motifs that possesses aggrecanase activity, ADAMTS11 (aggrecanase-2), which has extensive homology to ADAMTS4 (aggrecanase-1) and the inflammation-associated gene ADAMTS1. ADAMTS11 possesses a number of conserved domains that have been shown to play a role in integrin binding, cell-cell interactions, and extracellular matrix binding. We have expressed recombinant human ADAMTS11 in insect cells and shown that it cleaves aggrecan at the Glu(373)-Ala(374) site, with the cleavage pattern and inhibitor profile being indistinguishable from that observed with native aggrecanase. A comparison of the structure and expression patterns of ADAMTS11, ADAMTS4, and ADAMTS1 is also described. Our findings will facilitate the study of the mechanisms of cartilage degradation and provide targets to search for effective inhibitors of cartilage depletion in arthritic disease.

ADAM Proteins↗

Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins.

We purified, cloned, and expressed aggrecanase, a protease that is thought to be responsible for the degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)] is a member of the ADAMTS protein family that cleaves aggrecan at the glutamic acid-373-alanine-374 bond. The identification of this protease provides a specific target for the development of therapeutics to prevent cartilage degradation in arthritis.

ADAM Proteins↗

Instrumented measurement of anteroposterior and inversion-eversion laxity of the normal ankle joint complex.

Manual examination is the most common method for the evaluation of ankle anteroposterior (AP) and inversion-eversion (I-E) laxity. Objective assessment data of normal ankle laxity must be provided before comparison with an injured ankle can be made. The purpose of this study was to compare AP translation and I-E rotation at three force loads between dominant and nondominant ankles and to assess the test-retest reliability of a portable arthrometer in obtaining these measurements. The arthrometer consists of a frame that is fixed to the foot, a pad that is attached to the tibia, and a load-measuring handle that is attached to the foot plate through which the load is applied. A six-degrees-of-freedom spatial kinematic linkage system is connected between the tibial pad and the foot frame to measure motion. Instrumented measurement testing of total AP displacement and I-E rotation of both ankles was performed in 41 subjects (21 men and 20 women; mean age, 23.8 +/- 4.4 years). Subjects had no history of ankle injury. Subjects were tested in the supine position while lying on a table with the knee secured in extension and the foot positioned at 0 degrees of flexion. Laxity was measured from total AP displacement (millimeters) during loading to 125 N of AP force and from total I-E rotation (degrees of range of motion) during loading to 4000 N-mm. Reliability was evaluated by calculating intraclass correlation coefficients (2,1) at 75 N, 100 N, and 125 N of AP force and at 2000, 3000, and 4000 N-mm torque loads. Mean differences for displacement and rotation between the dominant and nondominant ankles at each of the force and torque loads were analyzed by dependent t-tests. For both the dominant and nondominant ankles, respectively, the reliability coefficients at each of the force loads for AP displacement (range, 0.82-0.89) and I-E rotation (range, 0.86-0.97) were high. The t-test analyses showed no significant differences (P > or = 0.05) for total AP displacement or I-E rotation between the dominant and nondominant ankles at any of the force loads. The results are clinically useful in providing information about the reliability of measures at different AP and I-E force loads using a portable ankle ligament arthrometer.

Adult↗

Analysis of a biodegradable composite for bone healing.

A degradable L-PLA/calcium carbonate composite made of interconnecting phases was examined. This structure was used both to slow the degradation rate and to reduce the brittleness of the ceramic. Both in vitro and in vivo degradation studies were performed. Samples were incubated in buffered saline or placed in the dorsum of rats for 0, 1, or 4 weeks. Mechanical testing was performed on both groups, volume fraction of each component was determined for in vitro samples, and histology was performed on in vivo samples. Failure load, tensile strength, and elastic modulus significantly decreased during the 1st week for both groups. Continued decreases were seen at 4 weeks for in vitro samples but not for in vivo. Failure strain and tensile strength decreased only for in vitro specimens. PLA fraction significantly decreased during the 1st week and then stabilized. Histology showed that tissue ingrowth occurred at 4 weeks. The decrease in mechanical properties was probably a result of the decreased PLA fraction. The stabilization and even a slight increase in tensile strength and failure strain in the in vivo samples was probably due to the tissue ingrowth forming an implant-tissue composite.

Animals↗

A six-degree-of-freedom test system for the study of joint mechanics and ligament forces.

A joint testing system was designed to transmit a specified motion or force to a joint in all six degrees of freedom (d.o.f.) using a spatial linkage system for position feedback. The precise reproducibility of position provided by this method of position feedback allows determination of in situ ligament forces for external joint loadings. Load on the structure of interest is calculated from six d.o.f. load cell output after the loaded position is reproduced with all other structures removed. In a test of this system, measured loads showed good agreement with applied loads.

Algorithms↗

Initial stability of porous coated acetabular implants. The effect of screw placement, screw tightness, defect type, and oversize implants.

The effects of screw location, screw tightness, acetabular bony defects, and implant size on the initial stability of porous coated acetabular implants was studied in vitro using 12 fresh frozen cadaver pelves. The fixation of porous coated acetabular implants was compared following fixation with either rim or center screws. Implants were tested first under axial and torsional stress. Then, either a peripheral or central bony defect was created in the acetabulum and testing was repeated in a similar fashion. Rim screws were noted to significantly improve the initial fixation of implants in intact acetabula and in acetabula with central bony defects. It was also shown that the tightness of the screws is an important factor affecting the strength of fixation. Although bony defects compromise the fixation of implants, specimens with central defects were very stable, particularly when tested with axial load. Acetabula with peripheral defects lost significant stability. The use of larger implants in acetabula with bony defects was shown to increase bony coverage and the overall implant stability.

Acetabulum↗

A biomechanical evaluation of an intramedullary fixation device for intertrochanteric fractures.

The strength and stability of an intramedullary device when used to fix intertrochanteric fractures were determined and compared with the dynamic hip screw (DHS). A standard four-part osteotomy was created in eight paired fresh frozen human cadaver femurs. The intramedullary fixation device and a DHS were implanted in each pair member, and mechanical testing was performed. Micromotion was measured during cyclic loading to determine implant stability, and then the specimens were loaded to failure. The intramedullary fixation device had significantly greater stability in cyclic loading than the DHS and required more than twice the force for failure. For patients with osteoporosis, this device may be a useful alternative to standard sliding nail systems.

Biomechanical Phenomena↗

The effects of knee motion and external loading on the length of the anterior cruciate ligament (ACL): a kinematic study.

A six-degrees-of-freedom mechanical linkage device was designed and used to study the unconstrained motion of ten intact human cadaver knees. The knees were subjected to externally applied varus and valgus (V-V) moments up to 14 N-m as well as anterior and posterior (A-P) loads up to 100 N. Tests were done at four knee flexion angles; 0, 30, 45, and 90 deg. Significant coupled axial tibial rotation was found, up to 21.0 deg for V-V loading (at 90 deg of flexion) and 14.2 deg for A-P loading (at 45 deg of flexion). Subsequently, the knees were dissected and the locations of the insertion sites to the femur and tibia for the anteromedial (AM), posterolateral (PL), and intermediate (IM) portions of the ACL were identified. The distances between the insertion sites for all external loading conditions were calculated. In the case when the external load was zero, the AM portion of the ACL lengthened with knee flexion, while the PL portion shortened and the intermediate (IM) portion did not change in length. With the application of 14 N-m valgus moment, the PL and IM portions of the ACL lengthened significantly more than the AM portion (p less than 0.001). With the application of 100 N anterior load, the AM portion lengthened slightly less than the PL portion, which lengthened slightly less than the IM portion (p less than 0.005). In general, the amount of lengthening of the three portions of the ACL during valgus and anterior loading was observed to increase with knee flexion angle (p less than 0.001).

Adult↗

Use of patellar tendon autograft for anterior cruciate ligament reconstruction in the rabbit: a long-term histologic and biomechanical study.

To assess the degree of success of anterior cruciate ligament (ACL) replacement using the patellar tendon (PT) autograft, 29 New Zealand white rabbits underwent ACL reconstruction using a medial one-third PT autograft. The femur-ligament-tibia complexes were evaluated at 0, 6, 30, and 52 weeks postoperatively for gross and histologic appearances and tensile load to failure properties. Grossly, the autografts did not resemble the control ACLs. Histologically, the autografts progressed from being hypercellular with a random collagen fiber bundle organization to having a near normal cellularity with a more parallel collagen fiber bundle pattern. Anteroposterior knee laxity was more than two times that of the control knees 52 weeks after reconstruction. Biomechanically, the PT autografts plateaued at 30 weeks postoperatively. The ultimate load and stiffness were 15 +/- 5% and 24 +/- 6% of the control ACLs, respectively. At 52 weeks, the appearance of the PT autograft had some general histologic similarities as compared with the native ACL. However, these similarities did not extend to the functional properties of the autograft.

Animals↗

A new device to measure the structural properties of the femur-anterior cruciate ligament-tibia complex.

Previous studies of biomechanical properties of femur-anterior cruciate ligament-tibia complex (FATC) utilized a wide variety of testing methodologies, particularly with respect to ligament orientation relative to loading direction. A new device was designed and built to test the anterior-posterior displacement of the intact porcine knee at 30 and 90 deg of flexion, as well as the tensile properties of the FATC at any loading direction and flexion angle. Tensile tests were performed with the knees at 30 and 90 deg of flexion with the loading direction along either the axis of the tibia (tibial axis) or the axis of the anterior cruciate ligament (ligament axis). The results showed that the stiffness, ultimate load and energy absorbed were all significantly increased when the FATC was tested along the ligament axis. This study demonstrates the importance of alignment in the evaluation of the biomechanical characteristics of the femur-ACL-tibia complex.

Animals↗

HCO emission from H II-molecular cloud interface regions.

A survey of well-known molecular clouds in the four strongest HCO NK-,K+ = 1(01)-0(00) hyperfine transitions has been carried out to determine the prevalence of HCO and to study its chemistry. HCO emission was observed in seven molecular clouds. Three of these, NGC 2264, W49, and NGC 7538, were not previously known sources of HCO. In addition, NGC 2024 and Sgr B2 were mapped and shown to have extensive HCO emission. The survey results show the HCO abundance to be enhanced in H II-molecular cloud interface regions and support a correlation between C+ and HCO emission. The strength of the HCO emission in NGC 2024 is interpreted in terms of this enhancement and the source structure and proximity to Earth.

Aldehydes↗

Sustained pressurization of polymethylmethacrylate: a comparison of low- and moderate-viscosity bone cements.

There is at present great uncertainty relating to the fixation of joint implants. The deficiencies of acrylic bone cement are well documented, but the limitations of cementless fixation are as yet imcompletely identified. The purpose of this study was to investigate the potential of sustained external pressurization to improve the mechanical characteristics of conventional acrylic bone cement. The effect of serially increasing sustained pressurization of two commerically available acrylic bone cements (Simplex-P and LVC) was evaluated in human cadaver femora. A new method for determination of the shear strength of the bone-cement interface in place of the traditional pushout tests was used. In this model, there was a significant increase in the bone-cement interfacial shear strength with increasing pressure, but no difference in the shear strength was found between the two cements. At all pressure levels, the shear strength of the cement was greater than that previously reported. Increased cement penetration into the cortical bone was demonstrated with increasing pressure and low-viscosity cement, but the extent of cement penetration did not correlate with the shear strength of the bone-cement interface.

Adult↗