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Biomedical subjects

P Guy

Publications and source records attributed to P Guy.

At least 19 recordsLinked to original sources

Femoral neck cortical geometry measured with magnetic resonance imaging is associated with proximal femur strength.

INTRODUCTION: Magnetic resonance imaging (MRI) is a promising medical imaging technique that we used to assess femoral neck cortical geometry. OBJECTIVES: Our primary objective was to assess whether cortical bone in the femoral neck assessed by MRI was associated with failure load in a simulated sideways fall, with and without adjustment for total bone size. Our secondary objective was to assess the reliability of the MRI measurements. MATERIALS AND METHODS: We imaged 34 human cadaveric proximal femora using MRI and dual-energy X-ray absorptiometry (DXA). MRI measurements of cross-sectional geometry at the femoral neck were the cortical cross-sectional area (CoCSA(MRI)), second area moment of inertia (x axis; Ix(MRI)), and section modulus (x axis; Zx(MRI)). DXA images were analyzed with the standard Hologic protocol. From DXA, we report the areal bone mineral density (aBMD(DXA)) in the femoral neck and trochanteric subregions of interest. The femora were loaded to failure at 100 mm/s in a sideways fall configuration (15 degrees internal rotation, 10 degrees adduction). RESULTS AND OBSERVATIONS: Failure load (N) was the primary outcome. We observed that the femoral neck CoCSA(MRI) and Ix(MRI) were strongly associated with failure load (r (2)=0.46 and 0.48, respectively). These associations were similar to those between femoral neck aBMD and failure load (r (2)=0.40), but lower than the associations between trochanteric aBMD and failure load (r (2)=0.70). CONCLUSION: We report that MRI holds considerable promise for measuring cortical bone geometry in the femoral neck and for predicting strength at the proximal femur.

Absorptiometry, Photon↗

Accuracy of pQCT for evaluating the aged human radius: an ashing, histomorphometry and failure load investigation.

INTRODUCTION: Quantifying the determinants of bone strength is essential to understanding if or how the structure will fail under load. Determining failure requires knowledge of material and geometric properties. However, characterizing the relative contributions of geometric parameters of bone to overall bone strength has been difficult to date because of limitations in imaging technology. Peripheral quantitative computed tomography (pQCT) uses digital images to derive estimates of bone strength in the peripheral skeleton and is a relatively safe technique to differentiate cortical from trabecular bone and assess bone geometry and density. However, in a compromised osteoporotic bone, thin cortices and low scan resolution can limit accurate analysis. METHODS: Therefore, in this two-part investigation we scanned ten pairs (n=20) of fresh-frozen radial specimens [female, mean (SD) age 79(6) years] using pQCT (XCT 2000) at the 4 and 30% sites of the distal radius. We investigated the accuracy of four different acquisition resolutions (200, 300, 400, 500 microm) and several analysis modes and thresholds. We evaluated (1) the accuracy of the Norland/Stratec XCT 2000 pQCT in assessing low-density bones by comparing pQCT outcomes to ashing and histomorphometry and (2) the association of geometric parameters by pQCT and areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) to failure load at the distal radius. RESULTS: Using histomorphometry and ashing as reference standards, we found that pQCT scans varied systematically and underestimated or overestimated total area and mineral content at the radial midshaft depending on the analysis algorithm and selected threshold. Overall, most pQCT analysis modes were accurate. In the mechanical testing studies, bone mineral content and cortical bone content at the midshaft were strongly associated with failure load. The pQCT parameters that best accounted for failure load were total content at the 4% site and cortical thickness at the 30% site and they accounted for up to 81% of the variance. The best DXA predictor of failure load was total density at the distal third site and it explained 75% of the variance. CONCLUSIONS: In summary, analysis mode, resolution and thresholding affected pQCT outputs at the radial midshaft. This study extends our understanding of pQCT analysis and provides important data regarding determinants of bone strength at the distal radius.

Aged↗

Comparison of Australian and international guidelines for grading severity of chronic obstructive pulmonary disease.

AIM: To compare grading of chronic obstructive pulmonary disease (COPD) using Australian guidelines Confirm diagnosis, Optimize function, Prevent deterioration, Develop a self-management plan and manage eXacerbations (COPD-X) versus Global initiative for Obstructive Lung Disease (GOLD) guidelines and to assess whether this is associated with differences in other health domains affected by COPD. Adult outpatients (n = 61) with COPD were studied using lung function measurements, six-minute walk test and body composition assessments. Subjects also completed self-rated dyspnoea scores and health-related quality-of-life scales. For each patient, COPD severity was graded using both COPD-X and GOLD guidelines, and results were collectively analysed. If significant discrepancies were observed, comparisons of other health domains were carried out. After grading severity using COPD-X and GOLD guidelines, significant discrepancies were noted. Of nine subjects with no disease (normal) based on COPD-X, seven were judged to be 'mild' according to GOLD. Similarly, 11 of 12 patients with mild disease (COPD-X) had 'moderate' disease judged by GOLD, and 9 of 23 with moderate severity (COPD-X) had 'severe' COPD using GOLD. Finally, 6 of 17 patients with COPD-X-rated severe disease had 'very severe' disease using the GOLD criteria. Among patients with COPD-X severe disease, those with GOLD discordant (very severe) severity had a poorer quality of life compared with those with GOLD concordant (severe) severity (P = 0.006). Similarly, there was also a trend towards lower six-minute walk test distance and greater subjective dyspnoea in GOLD very severe patients compared with GOLD severe patients. Significant discrepancies in grading of severity exist between Australian and international COPD guidelines. Current Australian guidelines for severity grading may not fully reflect the effect COPD has on other key domains of health.

Aged↗

The effectiveness of orthopaedic trauma theatres in decreasing morbidity and mortality: a study of 701 displaced subcapital hip fractures in two trauma centres.

In countries with universal health care systems patients frequently wait days for their "emergency" surgery. A general trend in orthopaedic traumatology is the advent of daily, dedicated orthopaedic trauma theatres. Availability of trauma theatres is believed to decrease morbidity and mortality, but this remains unproven. A retrospective review comparing morbidity and mortality outcomes between two similar level-one trauma centres (one without a dedicated trauma room system) was undertaken. We reviewed 701 elderly patients receiving hemiarthroplasties for displaced subcapital hip fractures over a 76-month period. Patients were similar between centres in terms of age, gender ratio and comorbidities. Statistically significant differences were found favouring the dedicated trauma room system with approximately half the operative delay and post-operative morbidity. A trend towards decreased mortality was also seen. This study supports the use of regular orthopaedic trauma theatres in tertiary care institutions.

Aged↗

Minimally invasive dynamic hip screw: prospective randomized trial of two techniques of insertion of a standard dynamic fixation device.

OBJECTIVE: This study evaluates the safety and outcome of a minimally invasive technique for inserting a standard dynamic hip screw for intertrochanteric fractures. HYPOTHESIS: The use of standard plate in a minimally invasive technique is both possible and advantageous to patient outcome. DESIGN AND METHODS: Prospective surgeon-randomized blinded outcome clinical study comparing new technique to conventional technique. MAIN OUTCOME MEASURE: Pain, operative time and mean hemoglobin drop in percutaneous hip fixation. RESULTS: The minimally invasive technique had significantly less blood loss (P < 0.001), operative time (P < 0.001) and a trend to less morphine use. CONCLUSIONS: Minimal invasive technique significantly reduces blood loss and operative time for fixation of intertrochanteric hip fractures without sacrifice of fixation stability or bone healing.

Aged↗

Evaluation of Escherichia coli DJ4309 expressing human P450 1A2 in mutagenicity testing of complex food mixtures.

Heterocyclic aromatic amines (HAAs) are potent bacterial mutagens and potential human carcinogens formed in heat processed proteins. The Ames test (strain TA98) is a useful mutagenicity test system to screen food products for these compounds. HAAs require activation to their genotoxic forms, and in the Ames test, a rat liver S-9 preparation is normally used. In order to better understand the mechanisms of mutagen activation with respect to human metabolism, new bacterial strains containing human cytochrome P450s and other metabolic enzymes have recently been developed. We have investigated the capacity of one of these strains, DJ4309 [Josephy et al., Chem. Res. Toxicol. 11 (1998) 70-74] as a screening tool for mutagens in food products. DJ4309 expresses the human P450 1A2, human NADPH cytochrome reductase and the bacterial acetyl CoA:arylamine N-acetyltransferase. This strain is as sensitive as the Ames system to the mutagenic effects of the heterocyclic aromatic amines 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline, but less sensitive to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. However, the mutagenicity of the arylamine 2-aminofluorene is considerably higher in DJ4309 than in the Ames test system. Meat extracts with a total HAA content ranging from less than 2 ng/g to 20 ng/g are efficiently detected by the Ames TA98 strain with rat liver S-9 activation. DJ4309 is less sensitive, with fewer revertants induced over the same dose range. Unknown compounds present in the meat extracts appear to inhibit the activity of the P450 1A2 enzyme in the DJ4309 strain. We have therefore demonstrated that although DJ4309 is a useful tool for mechanistic studies in chemical carcinogenesis, the screening of complex food matrices for HAAs by this bacterial strain must be conducted with caution.

Amines↗

Minimally invasive plate osteosynthesis: does percutaneous plating disrupt femoral blood supply less than the traditional technique?

OBJECTIVES/HYPOTHESIS: Proximal and distal femur fractures have traditionally been treated with open reduction and internal fixation through a standard lateral approach. New, "minimally invasive" internal fixation techniques, however, have been developed in an effort to devascularize the bone less than the traditional method. The purpose of this study was to determine whether a minimally invasive percutaneous plating technique better preserves bone vascularity relative to the traditional method by comparing the effect of the two approaches on the blood supply of the distal femur using silicone arterial dye injection in a cadaveric model. STUDY DESIGN/METHODS: Ten fresh human cadavers underwent lateral conventional plate osteosynthesis (CPO) through a standard lateral approach on one side and minimally invasive plate osteosynthesis (MIPO) through two three-centimeter incisions on the contralateral side. After injection of silicone dye, a dissection was performed bilaterally to identify the femoral perforating and nutrient arteries. RESULTS: All MIPO specimens showed intact perforating and nutrient arteries, whereas the CPO specimens had a variable incidence of vessel disruption. The MIPO group demonstrated better periosteal perfusion in each of the cadavers and improved medullary perfusion in 70 percent of the MIPO specimens compared with the CPO specimens. CONCLUSION: A percutaneous minimally invasive plating technique disrupts the femoral blood supply less than the traditional open method. Such minimally invasive methods may be more advantageous biologically than the traditional method.

Aged↗

CT-based analysis of the geometry of the distal femur.

When applying minimally invasive techniques (MIO, Minimally Invasive Osteosynthesis) to the fixation of the distal femur, the surgeon has access to a limited number of anatomical landmarks: namely the articular surface of the distal femur and a small portion of the distal lateral femoral cortex. A detailed knowledge of the local anatomy facilitates the technique and prevents complications. Using Kirschner wires placed at set positions in the distal femur, we analyzed the measurements obtained from the 3D reconstructed helical CT scans of 33 embalmed femora and we report on the anatomy of the distal femur as it relates to supracondylar fracture fixation.

Femur↗

Minimally invasive plate osteosynthesis and vascularity: preliminary results of a cadaver injection study.

A cadaver arterial injection study was performed to analyse the vascular supply to the femur and to study the effects of two surgical plating techniques on femoral vascularity. A 16-hole LC-DCP was applied on the intact femora of five fresh human cadavers. On one side, the plate was inserted using a conventional lateral plate osteosynthesis (CLPO) technique with elevation of the vastus lateralis muscle to expose the shaft. On the contralateral side, the plate was inserted percutaneously beneath the muscle using a minimally invasive plate osteosynthesis (MIPO) technique. After plating, blue silicone dye was injected through the common femoral artery. Cadaveric dissection was then performed to identify the femoral perforating arteries (PAs) and the nutrient artery (NA) of the femur. The pattern of periosteal filling and medullary perfusion of the injected dye was analysed and the topography of the PAs and NA was determined. CLPO placed the PAs and NA of the femur at risk. MIPO maintained the integrity of the PAs and NA and was associated with superior periosteal and medullary perfusion. The results of this study indicate that MIPO is superior to the CLPO in maintaining arterial femoral vascularity and perfusion.

Aged↗

New conformational properties induced by the replacement of Tyr-64 in Desulfovibrio vulgaris Hildenborough ferricytochrome c553 using isotopic exchanges monitored by mass spectrometry.

In order to study the conformational stability induced by the replacement of Tyr-64 in Desulfovibrio vulgaris Hildenborough (DvH) cytochrome c553, fast peptic digestion of deuterated protein followed by separation and measurement of related peptides using liquid chromatography coupled to electrospray ionization mass spectrometry was performed. We show that the H-bonding and/or solvent accessibility properties were modified by the single-site mutation. The mutant proteins can be classified into two groups: the Y64F and Y64L mutants with nearly unchanged deuterium incorporation compared to the wild-type protein and the Y64S, Y64V and Y64A mutants with increased deuterium incorporation. The 70-74 peptide was the most affected by mutation of Tyr-64, the phenylalanine mutant inducing slight stabilization whereas the serine mutant was significantly destabilized. In addition, from the analysis of the overlapping 37-57 and 38-57 peptides we can conclude that the amide proton of Tyr-38 has been replaced by deuterium in all proteins.

Cytochrome c Group↗

Stability study of Rhodobacter capsulatus ferrocytochrome c2 wild-type and site-directed mutants using hydrogen/deuterium exchange monitored by electrospray ionization mass spectrometry.

To estimate the stability of Rhodobacter capsulatus ferrocytochrome c2 wild-type and site-directed mutants, charge state distributions and hydrogen/deuterium exchange rates were monitored by electrospray ionization mass spectrometry. The relative stability of the mutants was observed with the order: V11 insert > Y75F > wild-type = K32E > K12D = K14E > or = K52E > K14E/K32E > W67Y > P35A > I57N > G34S. (A preliminary account has been presented for mutants G34S and P35A [Jaquinod et al. (1995) Rapid Commun. Mass Spectrom. 9, 1135-1140].) This approach is shown to be a useful tool for rapid characterization of mutational effects on protein conformation.

Cytochrome c Group↗

Study of the new stability properties induced by amino acid replacement of tyrosine 64 in cytochrome C553 from Desulfovibrio vulgaris Hildenborough using electrospray ionization mass spectrometry.

Hydrogen/deuterium exchange as well as charge state distribution monitored by electrospray ionization mass spectrometry were demonstrated to be a powerful and effective new tool for probing conformational properties of proteins in solution. In this paper, the influence of single amino acid replacements on the global conformation of cytochrome C553 from Desulfovibrio vulgaris Hildenborough using isotopic exchange monitored by electrospray ionization mass spectrometry is reported. Based on their respective charge state distributions and isotopic exchanges, we have differentiated relative stability of mutants and a ladder classification with the order being wild-type > Y64F = Y64L > Y64V > Y64A, under specific conditions of pH, is proposed.

Amino Acid Sequence↗

Unreamed intramedullary nailing of femoral shaft fractures: operative technique and early clinical experience with the standard locking option.

Nailing techniques have changed in recent years in ways which are not just limited to omitting the reaming process. These changes concern positioning patients, techniques of reduction and selecting implants. Techniques of approach and exposure have been modified to new, less-invasive procedures to fulfill technical, functional and cosmetic requirements. In addition, techniques have been developed to avoid fragment diastasis, rotational and sagittal malalignment, and leg-length discrepancy. Finally, simple algorithms have been elaborated for the management of specific fracture patterns (bilateral shaft fractures, ipsilateral tibial fractures or associated femoral neck fractures) and to determine the number and location of locking bolts. We developed these algorithms, techniques and procedures in a series of 133 femoral shafts, which were stabilized with the AO unreamed femoral nail (URFN) in a prospective study between 1991 and 1994. Of these, the first 57 cases with a mean follow-up of 17.9 months (range, 5-44) after injury were reviewed. Fractures were classified according to Müller's 1990 system: 12 type A, 29 type B and 16 type C. Closed soft-tissue injuries were classified by our classification of 1982: 17 type C 0/I, 42 type C II. Of 15 open fractures, six were OI, six OII, two OIIIA and one was OIIIB by Gustilo's classification of 1984. The major complications were two broken locking bolts, one nail breaking after 9 weeks, one case of osteitis and one of intra-operative lung embolism.

Adolescent↗

Intramural leiomyosarcoma of the dorsal pedal vein: a clinical mimicry of ganglion.

A 75-year-old woman presented with a ganglion-like nodule on the dorsal aspect of the right foot. A 2.5 x 1.5 cm, saccular and malleable tumor, that was in continuity with the dorsal venous arch, was completely resected. It was characterized by a diffuse intramural and circumferential, low grade, malignant, smooth muscle proliferation with an aneurysmal-like luminal space. No endoluminal or periadventitial invasive neoplastic component was present. The patient had no evidence of disease at 58-month follow-up. This is the first reported case of venous leiomyosarcoma in the foot. Furthermore, the intramural confinement of neoplastic growth is a unique observation.

Aged↗

Nucleotide sequence comparisons of turnip yellow mosaic virus isolates from Australia and Europe.

The genomic sequences of four isolates of turnip yellow mosaic virus (TYMV-Cd) from Australia, and three TYMV-1 (type) and three TYMV-2 (cauliflower) isolates from Europe were compared by cDNA-RNA hybridization tests, by analysis of the fragments produced from cDNA-RNA hybrids by restriction endonuclease treatment, and by determining the 3' terminal nucleotide sequences of their coat protein mRNAs. All three methods showed only slight differences (ca. 1%) between the mRNA sequences of different TYMV-1 and TYMV-Cd isolates, and did not distinguish between those groups of isolates. By contrast, the nucleotide sequences of TYMV-2 isolates differed from those of the other TYMVs by ca. 5% (sequence analysis) to 11% (restriction fragment analysis). Published biogeographic evidence has indicated that the TYMV-Cd and TYMV-1 populations probably separated more than 12,000 years ago. This implies that these TYMV genomes have changed at a rate of, at most, 1% in 10,000 years.

Australia↗

Severe tetanus complicating an open femoral fracture successfully managed using intrathecal human tetanus immunoglobulin and external fixation.

We report here a case of severe tetanus, complicating a compound fracture of the femur, successfully managed without intensive care facilities, using intravenous sedation and intrathecal Human Tetanus Immunoglobulin (HTI). Substitution of conventional traction (Transtibial Steinman Pin and Thomas Splint) for a Day Frame External Fixation Device (EFD) provided excellent fixation and stability of the fracture in spite of severe tetanic spasms.

Adolescent↗

The protein phosphatases involved in cellular regulation. 3. Fatty acid synthesis, cholesterol synthesis and glycolysis/gluconeogenesis.

The nature of the protein phosphatases involved in the regulation of glycolysis/gluconeogenesis, fatty acid synthesis and cholesterol synthesis in rat liver has been investigated using L-pyruvate kinase, ATP-citrate lyase, acetyl-CoA carboxylase and hydroxymethylglutaryl-CoA reductase as substrates. The results show that protein phosphatases-1, 2A and 2C are the only significant protein phosphatases in rat liver acting on these four substrates. The relationship of these three enzymes to other protein phosphatases described in the literature is discussed.

Animals↗