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Biomedical subjects

M Norton

Publications and source records attributed to M Norton.

At least 19 recordsLinked to original sources

[Femoral revision using cemented stem and compacted bone graft: femoral migration analysis].

PURPOSE OF THE STUDY: If the bone loss is significant, revision total hip arthroplasty can be most difficult. We present a series of 30 patients with major loss of bone stock treated with the X-change (Exeter) technique for revision total hip arthroplasty. MATERIAL AND METHODS: This prospective consecutive series included 30 reconstructions performed between 1996 and 2001. Compacted grafts with cryopreserved bone were used. Mean follow-up was 42 months (range 24-80). According to the SOFCOT classification, bone loss was stage II in one patient, stage III in 14 and stage IV in 15. The technique described by Gie, Linder and Ling was rigorously applied: smooth stem, no force on the Merckel, cement in the impacted allograft, filling of femoral bone defects. Reinforcement with plates, mesh, or wire was used as necessary to bridge cortical defects. The Postel-Merle-d'Aubigné (PMA) score was used to assess clinical outcome. Digital x-rays were obtained before and after surgery and at last follow-up to assess implant position (vertical migration and frontal deviation), changes in bone stock, and the Pierchon classification. Thirty patients were seen at two years follow-up. Two patients were lost to follow-up after two years. Material had to be removed in two patients because of mechanical intolerance. There was one postoperative fracture at six months. One patient died more than two years after implantation. The PMA score improved from 11 to 17 at last follow-up. Radiographic results showed mean 7.3 mm stem migration and mean 2 degrees frontal deviation which were not correlated with clinical presentation. The Pierchon classification revealed 20 situations of corticalization and eight of trabeculation. Factors affecting migration were modalities of graft preparation and time to first weight bearing. Migration was unchanged after twelve months. DISCUSSION AND CONCLUSION: The functional and radiographic results remained satisfactory in light of the initial bone loss. Implant migration did not affect outcome. We have modified the surgical technique in line with these results, particularly concerning preparation of the impacted bone graft. This technique has the advantage of filling bone defects and avoiding therapeutic escalation.

Adult↗

New evidence on birth spacing: promising findings for improving newborn, infant, child, and maternal health.

This editorial summarizes new evidence, some of which is published in this supplement, on birth spacing and newborn, infant, child and maternal health, as well as the demand for birth spacing services in the developing world. The article points to the high number of annual infant, child and maternal deaths, low birth weight infants and malnourished infants and children in developing countries. It highlights several new findings on birth spacing relevant to these conditions: It argues that, in light of the new evidence, birth spacing is an important, feasible and practical intervention to address these conditions and should be included in developing country health programs.

Attitude to Health↗

Detection of scarred and viable myocardium using a new magnetic resonance imaging technique: blood oxygen level dependent (BOLD) MRI.

BACKGROUND: The identification of viable myocardium in patients with impaired left ventricular contraction secondary to coronary heart disease is important clinically as such myocardium is likely to benefit from revascularisation. Blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) relies on changes in deoxyhaemoglobin concentration under stress for signal generation and could be used for the differentiation between scarred and viable myocardium. AIM: To assess the signal change on BOLD MRI in viable and scarred myocardium as identified by positron emission tomography (PET). METHOD: 19 patients with impaired left ventricular contraction and at least one akinetic area were enrolled. They underwent rest and dipyridamole stress MRI, using a double breath hold T2* weighted, ECG gated sequence to produce BOLD contrast images, and cine-MRI for wall thickening assessment. Dynamic perfusion and metabolic PET images followed the MRI. Signal change on BOLD MRI and the wall thickening were compared between rest and stress images in hibernating and scarred segments identified by PET on two short axis slices of mid ventricle, with eight segments each. RESULTS: Using PET, 68 segments were identified as hibernating and 42 as scarred. The hibernating segments were found on BOLD MRI to have an average signal change between rest and stress of -9.53%, compared with -2.15% in the scarred segments (p = 0.008). The average wall thickening was 8.7 mm in the hibernating segments compared with 5.9 mm in the scarred segments (p < 0.0001). CONCLUSIONS: BOLD MRI with wall thickening may differentiate scarred and viable myocardium and help identify suitable patients for revascularisation. Further larger studies are needed to establish a threshold for detection, sensitivity, and specificity.

Aged↗

Block allografts in revision total hip arthroplasty.

We report on 61 consecutive cemented acetabular revisions in which block allografts were used to reconstruct large defects. After a mean follow-up of 6.5 years, we observed satisfactory results when grafts had been rigidly fixed. Additional buttress-plates can improve the outcome. Paprosky type 3B defects had a double risk of failure. Cup migration had a 56% predictive value for failure. Several metal-backed cups failed, although the graft remained intact. There was a good improvement in functional outcome, which did not deteriorate up to a maximum follow-up of 11 years. Cemented revision total hip arthroplasty with the use of block allografts can give acceptable results in the medium to long term.

Acetabulum↗

Concentration-dependent phorbol stimulation of PKCalpha localization at the nucleus or subplasmalemma in A7r5 cells.

The subcellular translocation of PKCalpha was studied in A7r5 cells by confocal microscopy through use of standard immunohistologic staining and PKCalpha-enhanced green fluorescent protein (PKCalpha-EGFP) fusion protein expression. The results from both methods were consistent in indicating that PKCalpha, observed to be diffusely distributed in the unstimulated cell, was translocated primarily to either the perinuclear region of the cell or to subplasmalemmal sites depending on the concentration of phorbol 12, 13 dibutyrate (PDBu) used to activate the response. Translocation of PKCalpha to the perinucleus but not the plasmalemma was blocked by the use of colchicine to disrupt cell microtubules. However, there was little evidence of significant colocalization of PKCalpha with the microtubular cytoskeleton during the interval of translocation. By comparison, cytochalasin B disruption of actin microfilaments had no significant effect on PKCalpha translocation to either the plasmalemma or the perinucleus. The results indicate that the target site of PKCalpha translocation may vary with activating stimulus strength in A7r5 cells and that the translocation of the isoform to perinuclear target loci depends on an intact microtubular cytoskeleton. This suggests that multiple pathways are available for the redistribution of PKCalpha that may employ different mechanisms to regulate the movement and/or docking of the isoform at specific target sites.

Animals↗

Constancy of masseter muscle structure and function with age in F344 rats.

Senile muscle atrophy is a characteristic feature of advancing age. Despite the growing body of knowledge about weight-bearing muscles in rodents and man, there is relatively little such information on the muscles of mastication. Therefore, the primary goal here was to develop a masseter muscle preparation from male Fischer 344 rats suitable for studying contractile characteristics in vitro. And, secondarily, the goal was to examine this preparation for evidence of age-related changes in muscle composition and function in rats aged 4--24 months. Histochemical analysis of the composition of the four anatomical regions (branches) of the masseter revealed a mixture of rapidly contracting, fatiguable and fatigue-resistant muscle fibres with no significant differences between branches. Fibre type and size were determined with myosin ATPase, NADH-TR and toluidine blue staining of quick- frozen muscle sections. No significant changes in fibre type or fibre area were found with increasing age. One branch of the masseter, the anterior deep masseter, is sufficiently thin (less than 0.8 mm thickness) for adequate diffusion of oxygen and nutrients in studies of isometric contractile properties in vitro. Contraction time, half-relaxation time, dry weight:wet weight ratio and maximum force per unit area were found to be similar in muscles of young and old rats. Our results demonstrate that the anterior deep masseter of the rat is a suitable preparation for investigating masseter function in vitro. The surprising absence of age-related changes in composition and function is consistent with some, but not all, data on ageing rodent limb muscles. The results suggest that masticatory muscle performance is preserved with age in rats.

Aging↗

Relationship of twin zygosity and risk of preeclampsia.

OBJECTIVE: Twin gestations are known to be at higher risk for preeclampsia. One theory suggests that maternal recognition of fetal and trophoblastic tissues as foreign may be a factor. If that hypothesis is true, mothers carrying monozygous (MZ) gestations (ie a single fetal graft) might be predicted to have a lower rate of preeclampsia than those carrying dizygous (DZ) gestations. To evaluate this hypothesis, we compared the rate of preeclampsia in mothers with MZ and DZ twin gestations. STUDY DESIGN: Seven hundred sixty-eight twin deliveries from 1994 to 1999 were reviewed. Placental pathology reports were reviewed to determine the chorionic state of each placenta. Monochorionic placentas were assumed to be MZ. Dichorionic placentas were categorized as DZ if the neonates were of different sexes or different blood types. Maternal and fetal data were abstracted from the medical records. Preeclampsia was defined by standard criteria of the National Institutes of Health Working Group on High Blood Pressure. Our analysis was limited to women with pregnancies reaching at least 30 weeks of gestation where zygosity could be determined. RESULTS: Our analysis included 464 twin pregnancies, 154 MZ and 310 DZ. Among nulliparous women, the rate of preeclampsia was 15% (25/170) for DZ twins versus 20% (15/75) for MZ twins (P =.3). Among multiparous women, the rate was 8% (11/140) for DZ twins and 5% (4/79) for MZ twins (P =.4). In a logistic regression performed to control for confounding by maternal age, gestational age at delivery, assisted reproduction, and male sex, dizygotic state was associated with an odds ratio of 1.4 (95% CI = 0.5-3.9) for developing preeclampsia in nulliparous women and 1.2 in multiparous women (95% CI = 0.3-5.0). CONCLUSIONS: : These results do not support the hypothesis that zygosity affects the rate of preeclampsia in twin gestations, though the number of subjects in our study was too small to allow definitive conclusions. Larger studies are needed to evaluate this finding.

Adult↗

Assessing the risk of sudden cardiac death.

Detection of a major risk factor for sudden death in an otherwise asymptomatic person often raises major difficulties in management, particularly where the only treatment available is invasive, such as the implantable defibrillator. Recent guidelines have described the appropriate use of this technology, but often difficulty remains. This is particularly the case where the condition is newly recognised and its natural history not yet extensively described. A 63 year old man, whose condition was diagnosed as Brugada syndrome, in whom this problem is illustrated is described.

Arrhythmias, Cardiac↗

Three-dimensional graphic reconstruction of the insect exoskeleton through confocal imaging of endogenous fluorescence.

The exoskeleton of the cockroach leg was imaged via confocal microscopy to generate digital graphic reconstructions of its three-dimensional structure. The cuticle is autofluorescent and can be visualized without staining, but is maximally imaged in aldehyde-fixed preparations viewed under krypton-argon laser illumination (yellow green (568 nm) excitation, commonly used in confocal microscopes). Images of the entire trochanteral segment of the leg were constructed as montages from optical sections taken as overlapping series that were coincident in the z-axis. Reconstructions of the exoskeleton from these images showed that strain sensing mechanoreceptors are located in association with buttresses and thickenings that form a consistent internal architecture in both juvenile and adult animals. Accuracy of reconstructions was gauged by embedding specimens in Spurr's resin and histologically sectioning them perpendicular to the optical plane of section (z-axis). Comparison of plastic sections with two-dimensional images generated by "resectioning" the software model showed that reconstructed exoskeleton had a high level of accuracy. Imaging of older and larger animals was limited by the sclerotization and increased thickness of the cuticle. Surface extraction algorithms were used to generate vector graphic files in CAD format for export to software used in engineering and design. Among other potential uses, these models have been studied by Finite Element Analysis to examine the distribution of mechanical strains in the exoskeleton that occur during posture and locomotion. The advantages and limitations of the techniques are discussed. These methods may be used in studying the exoskeleton and the anatomy of cuticular mechanoreceptors of other arthropods to similar advantage.

Animals↗

PKCalpha translocation is microtubule-dependent in passaged smooth muscle cells.

The translocation of protein kinase C (PKC) isozymes from their inactive cell locus to a variety of cytoskeletal, organelle, and plasmalemmal sites is thought to play an important role in their activation and substrate specificity. We have utilized confocal microscopy to compare phorbol 12, 13 dibutyrate (PDB) - stimulated translocation of PKCalpha in cultured cells derived from rat vascular smooth muscle. In enzymatically dispersed, passaged smooth muscle cells, PKCalpha was uniformly distributed throughout the unstimulated cell. PDB stimulation resulted in extensive association of the PKCalpha into filamentous strands with subsequent accumulation of the isoform in the peri-nuclear region of the cell. Dual immunostaining indicated that PKCalpha was extensively colocalized with microtubules in the interval immediately following PDB stimulation but was largely disassociated from microtubules at 10 min, at which time the translocation of PKCalpha to the peri-nucleus/nucleus was nearly complete. It was further found that the use of colchicine to disrupt the microtubules caused the loss of PKCalpha translocation to the peri-nuclear region. By comparison, cytochalasin B disruption of actin microfilaments had no significant effect on this parameter. The data suggest that PDB stimulation results in a transient association of PKCalpha with cell microtubules and that the microtubules play an important role in the translocation of PKCalpha from the cytosol in passaged cells derived from rat aortic smooth muscle.

Actin Cytoskeleton↗

Three-dimensional echocardiographic reconstruction of mitral valve color Doppler flow events.

In vitro studies have suggested superior accuracy of 3-dimensional echocardiography over conventional methods for the characterization and quantitation of color Doppler flow events. Little in vivo work has been reported in this area; this study demonstrates the feasibility of 3-dimensional reconstruction of mitral valve flow events in an unselected group of adult patients and discusses optimal instrument settings for the acquisition of 3-dimensional datasets.

Adult↗

The relation between surface roughness and interfacial shear strength for bone-anchored implants. A mathematical model.

A rough bone implant surface was conceptualized as being built up of pits of different sizes and of different shapes. Hypotheses were formulated regarding the mechanical strength of the interfacial bone based upon the present knowledge of the character of the tissues adjacent to endosseous implants and the mechanical characteristics of different bone constituents. A surface roughness parameter was derived, the pit effectivity factor (fpe), which describes how effective the individual pits of the rough surface are as retention elements with regard to shear. Another surface roughness parameter was defined, the pit density factor (fpd), the value of which depends upon how densely packed the pits are. The interfacial shear strength of a rough implant surface with known microgeometry can be estimated by means of these two surface roughness parameters. The effectiveness of pits of different sizes and of different shapes was investigated using this model.

Algorithms↗

Dobutamine stress echocardiography: improved endocardial border definition and wall motion analysis with tissue harmonic imaging.

BACKGROUND: We performed a study to determine whether tissue harmonic imaging (THI) facilitates wall motion analysis at rest and whether these benefits extend through the stages of a dobutamine stress echocardiography (DSE) study. We also assessed the impact of THI on the feasibility of DSE in technically difficult patients. Finally we tested the hypothesis that THI by improving endocardial border definition (EBD) could enhance the interobserver agreement between trainees and experienced operators for interpreting DSE studies. METHODS: Twenty unselected patients underwent DSE by standard protocol. Parasternal and apical views were obtained with the use of fundamental mode (FND) and THI at baseline, low dose, and peak stress. Segmental EBD was characterized as 1 to 4 (1 = excellent) and segmental wall motion was characterized as 1 to 4/x (1 = normal, x = unable to interpret) by a consensus of 2 experienced observers. A trainee in stress echocardiography independently scored all segments, and these results were compared with the consensus of the experienced readers. RESULTS: EBD improved with THI in 26 +/- 6.7 of 48 segments per patient (54%, 95% confidence interval [CI] 0.40 to 0.68) and deteriorated with THI in only 2 +/- 2.7 (4%, 95% CI 0 to 0.09). Of the total of 48 segments per patient, a mean of 10 +/- 5.7 (21%, 95% CI 0.10 to 0.31) were of inadequate quality to be interpreted for wall motion on FND, and this changed to 4 +/- 3.4 (6%, 95% CI 0.06 to 0.12) on THI (P <.001). EBD improved in a similar degree in all DSE stages 53%, 54%, and 53% for rest, low dose, and peak stress, respectively. Six of the 20 study patients were deemed unsuitable for DSE on FND, and all were changed to suitable subjects on THI. Of the 205 segments deemed unsuitable for interpretation on FND, 140 (68%) were of the anterior and lateral walls of the LV. Improvement with THI was also more prominent on these walls. The mean coefficient of agreement (kappa) for wall motion analysis was 0.82 +/- 0.14 on FND and improved to 0. 92 +/- 0.09 on THI (P <.001). CONCLUSIONS: THI dramatically improves EBD and the ability to confidently score segmental wall motion. Interobserver agreement is also significantly enhanced. These benefits extend to the peak stage of a DSE study. Routine use of THI may enhance the diagnostic accuracy of DSE and extend its application to technically difficult patients previously deemed unsuitable.

Adult↗

Preliminary study of the incidence of disomy in sperm fractions after MicroSort flow cytometry.

Using triple colour fluorescent in-situ hybridization (FISH) we have evaluated, on a blind basis, the disomy level for chromosome 21 and the sex chromosomes in flow cytometric sorted sperm samples. There were no statistically significant differences in the disomy rates when comparing the sorted samples (either for X- or Y-bearing spermatozoa) with non-sorted samples. There were no diploid spermatozoa observed in any sample group after MicroSort processing.

Adult↗

Evaluation of 18F-FDG positron emission tomography in gastric and oesophageal carcinoma.

The aim of this study was to evaluate 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) in gastric and oesophageal carcinoma. 16 patients with biopsy proven oesophageal or gastric carcinoma had PET scans. Four patients had advanced disease and received palliative treatment. The remaining 12 patients were randomized to immediate surgery or neoadjuvant chemotherapy. Three patients had repeat PET scans following chemotherapy. PET detected the primary tumour in all cases including stage T1 lesions. Involved locoregional nodes (N1, N2) were not identified separately from the primary tumour. Semiquantitative analysis was performed in the form of tumour to liver activity ratios (TLR). In general, the TLR values were higher in the higher T stages, although there was only one case each of T1 and T2 lesions. PET scanning using 18F-FDG is a sensitive method for detecting primary oesophageal and gastric cancers but is limited in locoregional staging.

Adult↗