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1.
Nurs Leadersh (Tor Ont) ; 36(2): 58-71, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37917345

ABSTRACT

As the number of people with dementia admitted to hospitals is expected to grow, now is the time to identify methods to improve nursing care of this population. We conducted an environmental scan to identify and describe interventions in Canadian hospitals to improve the nursing care of people with dementia, how they are being evaluated and what issues influence the success of interventions. Methods included a search of published and unpublished literature and key stakeholder interviews. Interventions are described under three categories: (1) interventions to improve nurses' knowledge, attitudes and skills; (2) interventions to address responsive behaviours; and (3) interventions to help nurses individualize care. The evaluation of interventions rarely included an evaluation of effectiveness and more often included a qualitative evaluation of nurses' experiences with interventions. We summarize the factors affecting the implementation of interventions following the Consolidated Framework for Implementation Research (Damschroder et al. 2009) and suggest strategies for supporting the success of interventions to improve patient care and the experiences of nurses working with people with dementia.


Subject(s)
Dementia , Nurses , Nursing Care , Humans , Clinical Competence , Canada , Hospitals , Qualitative Research
2.
JBI Evid Synth ; 20(3): 899-906, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34719660

ABSTRACT

OBJECTIVE: This review will focus on the effectiveness of, and experience with, nursing interventions to improve the care of people with dementia in hospital. INTRODUCTION: Acute care for people with dementia has been identified as an area for improvement. Admission to hospital can be upsetting and difficult for people with dementia and can be associated with negative outcomes. Nurses play a significant role in shaping the experience of hospitalization and are the focus of many related interventions. INCLUSION CRITERIA: This mixed methods review will examine literature on improving acute care for people with dementia. The quantitative component will consider studies that evaluate nursing interventions to improve care of people with dementia, comparing the intervention with usual care, other therapies, or no comparator. Outcomes will include behavioral, health, and health system indicators. The qualitative component will consider studies that explore the experience of nursing interventions from the perspective of people with dementia, their family- or friend-caregivers, and nurses. METHODS: This review will be conducted in accordance with JBI methodology for mixed methods systematic reviews. Twelve databases and gray literature sources will be searched for published and unpublished studies. Titles, abstracts, and full-text selections will be screened by two or more independent reviewers and assessed for methodological validity using the standard JBI critical assessment tools. This review will follow a convergent segregated approach to data synthesis and integration. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021230951.


Subject(s)
Caregivers , Dementia , Critical Care , Delivery of Health Care , Dementia/therapy , Hospitals , Humans , Review Literature as Topic
3.
Ophthalmology ; 124(9): 1392-1402, 2017 09.
Article in English | MEDLINE | ID: mdl-28461018

ABSTRACT

PURPOSE: To determine whether: (1) change in lamina cribrosa depth occurs more frequently than change in neuroretinal parameters in glaucoma, and (2) Bruch's membrane or anterior sclera should be used as a reference plane when measuring laminar depth. DESIGN: Prospective observational study. PARTICIPANTS: One hundred fifty-five glaucoma patients and 35 healthy controls. METHODS: Anterior laminar depth from a Bruch's membrane (LD-BM) or anterior sclera (LD-AS) reference plane were measured with optical coherence tomography. Two neuroretinal parameters, minimum rim width and retinal nerve fiber layer thickness, in addition to peripapillary choroidal thickness were measured. Factors related to laminar depth were determined with mixed-effects modeling. Cutoffs for significant change in each parameter were estimated from variability in healthy controls over 1 year. The occurrences of significant change in laminar depth and neuroretinal parameters were compared with survival models. Because normal aging has a clear effect on neuroretinal parameters, but not on laminar depth, changes in neuroretinal parameters were adjusted for age-related reduction. MAIN OUTCOME MEASURES: Longitudinal changes in laminar depth and neuroretinal parameters. RESULTS: Glaucoma patients were followed up for a mean of 3.90 years (range, 2.03-5.44 years). The LD-BM was influenced significantly more by choroidal thickness (1.14 µm/µm; 95% confidence interval, 1.07-1.21) than was the LD-AS (0.15 µm/µm; 95% confidence interval, 0.08-0.22). Posterior movement of the lamina (LD-BM increase or LD-AS increase) occurred with the same frequencies as thinning in neuroretinal parameters. Anterior movement of the lamina was detected more frequently with the Bruch's membrane (LD-BM decrease) compared with the anterior sclera (LD-AS decrease) reference plane (hazard ratio, 3.23; P < 0.01). Significant choroidal thinning occurred in most patients (25/28 [89%]) in whom anterior movement of the lamina occurred with the Bruch's membrane, but not the anterior sclera, reference plane (LD-BM decrease without LD-AS decrease). Patients had a wide range of individual rates of change of choroidal thickness, from -20.00 to 17.09 µm/year (mean, -1.62 µm/year). CONCLUSIONS: Lamina cribrosa depth should be measured from an anterior sclera reference plane to reduce the influence of choroidal thickness changes. In glaucoma patients, lamina cribrosa depth changes are detected with similar frequency as neuroretinal parameter changes.


Subject(s)
Choroid/pathology , Glaucoma, Open-Angle/diagnosis , Nerve Fibers/pathology , Optic Disk/pathology , Optic Nerve Diseases/diagnosis , Retinal Ganglion Cells/pathology , Aged , Aged, 80 and over , Anatomic Landmarks , Bruch Membrane/anatomy & histology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Observer Variation , Prospective Studies , Reproducibility of Results , Sclera/anatomy & histology , Tomography, Optical Coherence/methods , Visual Field Tests , Visual Fields/physiology
4.
Ophthalmology ; 123(9): 1949-56, 2016 09.
Article in English | MEDLINE | ID: mdl-27432205

ABSTRACT

PURPOSE: To determine whether structural abnormalities of the lamina cribrosa explain the presence of optic disc hemorrhages, we determined the spatial concordance between disc hemorrhages and laminar disinsertions from the sclera. DESIGN: Prospective noninterventional study. PARTICIPANTS: From open-angle glaucoma patients followed up prospectively, we identified 52 eyes of 46 open-angle glaucoma patients with optic disc hemorrhage (ODH+ group) in at least 1 optic disc photograph during follow-up. We also identified 52 control eyes of 46 glaucoma patients in whom no disc hemorrhage was detected (ODH- group). METHODS: Enhanced depth imaging optical coherence tomography of the optic nerve head (24 radial scans) was performed. The scans were de-identified and a trained observer masked to all clinical information determined the presence of laminar disinsertions in each of the 48 positions with a confidence score of 1 (least certain) to 5 (most certain). Only disinsertions with a score of 3 or more were included in the analysis. MAIN OUTCOME MEASURES: Frequency and spatial concordance between disc hemorrhages and laminar disinsertions. RESULTS: The median age, visual field mean deviation, and follow-up period of the ODH+ and ODH- groups was 77.5 and 70.8 years, -5.20 and -4.70 dB, and 10.4 and 9.9 years, respectively. There were 84 hemorrhages recorded in the ODH+ group. There were laminar disinsertions in 50 eyes (96%) in the ODH+ group and in 27 eyes (52%) in the ODH- group, with 2 or more disinsertions in 30 eyes (58%) and 5 eyes (10%), respectively. Most hemorrhages and disinsertions were located in the inferotemporal and superotemporal sectors. However, in individual patients, only 33 of the ODHs (39%) were located within a laminar disinsertion. CONCLUSIONS: Laminar disinsertions occurred twice as frequently in eyes with ODHs; however, in individual patients, the spatial concordance between ODHs and laminar disinsertions was poor.


Subject(s)
Glaucoma, Open-Angle/complications , Optic Disk/pathology , Retinal Hemorrhage/etiology , Aged , Aged, 80 and over , Female , Glaucoma, Open-Angle/pathology , Humans , Male , Middle Aged , Prospective Studies , Retinal Hemorrhage/pathology , Tomography, Optical Coherence
5.
Invest Ophthalmol Vis Sci ; 57(7): 3103-11, 2016 06 01.
Article in English | MEDLINE | ID: mdl-27294804

ABSTRACT

PURPOSE: To determine whether beta and gamma peripapillary atrophy (PPA) areas measured with optical coherence tomography (OCT) enhances glaucoma diagnosis in myopic subjects. METHODS: We included 55 myopic glaucoma patients and 74 myopic nonglaucomatous controls. Beta-PPA comprised the area external to the clinical disc margin, with absence of retinal pigment epithelium and presence of Bruch's membrane. Gamma-PPA comprised the area external to the disc margin, with absence of both RPE and Bruch's membrane. OCT scans colocalized to fundus photographs were used to measure PPA, choroidal thickness, border tissue of Elschnig configuration, optic disc area, and optic disc ovality. RESULTS: Beta-PPA area was larger in glaucoma patients compared with controls (median [interquartile range], 1.0 [0.66-1.53] mm2 and 0.74 [0.50-1.38] mm2, respectively), whereas gamma-PPA was smaller in glaucoma patients compared with controls (0.28 [0.14-0.50] mm2 and 0.42 [0.17-0.74] mm2, respectively). However, the distributions of both beta- and gamma-PPA in the two groups overlapped widely. The areas under the receiver operating characteristic curve of beta- and gamma-PPA areas were 0.60 and 0.59, respectively. Larger beta-PPA area was associated with larger disc area, thinner choroidal thickness, longer axial length, less oblique border tissue configuration, older age, and greater disc ovality. Larger gamma-PPA area was associated with greater disc ovality, more oblique border tissue configuration, and longer axial length. CONCLUSIONS: Subclassifying PPA with OCT into beta and gamma zones reveals association with different covariates, but does not enhance the diagnostic performance for glaucoma in a population of predominantly Caucasians myopic subjects.


Subject(s)
Glaucoma/diagnosis , Myopia/pathology , Optic Atrophy/pathology , Tomography, Optical Coherence/methods , Aged , Case-Control Studies , Choroid/pathology , Eye Diseases, Hereditary/diagnosis , Female , Glaucoma/pathology , Humans , Male , Middle Aged , Optic Disk/pathology
6.
Ophthalmology ; 123(6): 1181-9, 2016 06.
Article in English | MEDLINE | ID: mdl-26992843

ABSTRACT

PURPOSE: Ruling out glaucoma in myopic eyes often poses a diagnostic challenge because of atypical optic disc morphology and visual field defects that can mimic glaucoma. We determined whether neuroretinal rim assessment based on Bruch's membrane opening (BMO), rather than conventional optic disc margin (DM)-based assessment or retinal nerve fiber layer (RNFL) thickness, yielded higher diagnostic accuracy in myopic patients with glaucoma. DESIGN: Case-control, cross-sectional study. PARTICIPANTS: Myopic patients with glaucoma (n = 56) and myopic normal controls (n = 74). METHODS: Myopic subjects with refraction error greater than -2 diopters (D) (spherical equivalent) and typical myopic optic disc morphology, with and without glaucoma, were recruited from a glaucoma clinic and a local optometry practice. The final classification of myopic glaucoma or myopic control was based on consensus assessment by 3 clinicians of visual fields and optic disc photographs. Participants underwent imaging with confocal scanning laser tomography for measurement of DM rim area (DM-RA) and with spectral domain optical coherence tomography (SD OCT) for quantification of a BMO-based neuroretinal rim parameter, minimum rim width (BMO-MRW), and RNFL thickness. MAIN OUTCOME MEASURES: Sensitivity of DM-RA, BMO-MRW, and RNFL thickness at a fixed specificity of 90% and partial area under the curves (pAUCs) for global and sectoral parameters for specificities ≥90%. RESULTS: Sensitivities at 90% specificity were 30% for DM-RA and 71% for both BMO-MRW and RNFL thickness. The pAUC was higher for the BMO-MRW compared with DM-RA (P < 0.001), but similar to RNFL thickness (P > 0.5). Sectoral values of BMO-MRW tended to have a higher, but nonsignificant, pAUC across all sectors compared with RNFL thickness. CONCLUSIONS: Bruch's membrane opening MRW is more sensitive than DM-RA and similar to RNFL thickness for the identification of glaucoma in myopic eyes and offers a valuable diagnostic tool for patients with glaucoma with myopic optic discs.


Subject(s)
Diagnostic Techniques, Ophthalmological , Glaucoma, Open-Angle/diagnosis , Myopia/diagnosis , Nerve Fibers/pathology , Optic Disk/pathology , Optic Nerve Diseases/diagnosis , Retinal Ganglion Cells/pathology , Area Under Curve , Bruch Membrane/pathology , Case-Control Studies , Cross-Sectional Studies , Diagnostic Techniques, Ophthalmological/standards , False Negative Reactions , Female , Humans , Intraocular Pressure , Male , Microscopy, Confocal/standards , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Sensitivity and Specificity , Tomography, Optical Coherence/standards , Vision Disorders/diagnosis , Visual Fields
7.
Invest Ophthalmol Vis Sci ; 57(1): 181-7, 2016 Jan 01.
Article in English | MEDLINE | ID: mdl-26795824

ABSTRACT

PURPOSE: To compare the diagnostic accuracy of conventional sector-based analysis with a method devised to detect the smallest localized neuroretinal rim and retinal nerve fiber layer thickness (RNFLT) damage. METHODS: One eye of 151 glaucoma patients and 83 healthy controls (median age and MD, 71.7 and 66.7 years, and -3.6 and -0.3 dB, respectively) was imaged with spectral-domain optical coherence tomography (OCT). Bruch's membrane opening-minimum rim width (BMO-MRW) and RNFLT were determined at 1° intervals and also averaged for each sector. A classification of glaucoma was made with sectoral analysis when the sectoral value was below the 1%, 5%, or 10% normative limit (from an independent normative dataset); and with total analysis when a given number of measurements was below the 1%, 5%, or 10% normative limit. RESULTS: With the 1% normative limit, BMO-MRW sectoral analysis yielded sensitivity of 87% and specificity of 92%; while at the same specificity (92%), total analysis yielded sensitivity of 88%. With RNFLT, sectoral analysis yielded sensitivity of 85% and specificity of 95%; while at the same specificity (95%), total analysis yielded sensitivity of 83%. The results for the 5% and 10% normative limits yielded lower specificity but higher sensitivity. In the whole glaucoma population, none of the sensitivity values of the sectoral and total analysis at the same specificities were statistically different. CONCLUSIONS: The diagnostic accuracy of sectoral analysis was equivalent to total analysis. These results indicate that BMO-MRW and RNFLT defects were wide and deep enough for detection by conventional sectoral analysis.


Subject(s)
Glaucoma, Open-Angle/diagnosis , Optic Disk/pathology , Retinal Ganglion Cells/pathology , Tomography, Optical Coherence/methods , Aged , Female , Glaucoma, Open-Angle/physiopathology , Humans , Intraocular Pressure , Male , Middle Aged , Reproducibility of Results , Visual Fields
8.
Ophthalmology ; 122(12): 2392-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26421707

ABSTRACT

PURPOSE: To describe longitudinal rates of change of neuroretinal parameters in patients with glaucoma and healthy controls, and to evaluate the influence of covariates. DESIGN: Prospective longitudinal study. PARTICIPANTS: Treated patients with glaucoma (n = 192) and healthy controls (n = 37). METHODS: Global disc margin-based neuroretinal rim area (DMRA) was measured with confocal scanning laser tomography, while Bruch's membrane opening-minimum rim width (BMO-MRW), BMO area (BMOA), and peripapillary retinal nerve fiber layer thickness (RNFLT) were measured with optical coherence tomography at 6-month intervals. Individual rates of change were estimated with ordinary least-squares regression, and linear mixed effects modeling was used to estimate the average rate of change and differences between the groups, and to evaluate the effects of baseline measurement and baseline age on rates of change. MAIN OUTCOME MEASURES: Rates of change for each parameter. RESULTS: Subjects were followed for a median (range) of 4 (2-6) years. The proportion of controls who had significant reduction of neuroretinal parameters was 35% for BMO-MRW, 31% for RNFLT, and 11% for DMRA. The corresponding figures for patients with glaucoma were not statistically different (42%, P = 0.45; 31%, P = 0.99; 14%, P = 0.99, respectively). Controls had a significant reduction of BMO-MRW (mean: -1.92 µm/year, P < 0.01) and RNFLT (mean: -0.44 µm/year, P = 0.01), but not DMRA (mean: -0.22×10(-2) mm(2)/year, P = 0.41). After adjusting for covariates, patients with glaucoma had faster, but not statistically different, rates of deterioration compared with controls, by -1.26 µm/year (P = 0.07) for BMO-MRW, -0.40 µm/year (P = 0.11) for RNFLT, and -0.38×10(-2) mm(2)/year (P = 0.23) for DMRA. Baseline BMO-MRW and RNFLT significantly influenced the respective rates of change, with higher baseline values relating to faster reductions. Older age at baseline was associated with a slower reduction in rates of BMO-MRW. Reductions in intraocular pressure were related to increases in BMO-MRW and DMRA. There was a tendency for BMOA to decrease over time (-0.38×10(-2) mm(2)/year; P = 0.04). CONCLUSIONS: Age-related loss of neuroretinal parameters may explain a large proportion of the deterioration observed in treated patients with glaucoma and should be carefully considered in estimating rates of change.


Subject(s)
Aging/physiology , Glaucoma, Open-Angle/physiopathology , Nerve Fibers/pathology , Optic Disk/pathology , Optic Nerve Diseases/physiopathology , Retinal Ganglion Cells/pathology , Aged , Female , Follow-Up Studies , Glaucoma, Open-Angle/surgery , Healthy Volunteers , Humans , Intraocular Pressure/physiology , Male , Microscopy, Confocal , Middle Aged , Optic Nerve Diseases/surgery , Prospective Studies , Tomography, Optical Coherence , Visual Field Tests
9.
Ophthalmology ; 119(2): 294-303, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22133797

ABSTRACT

PURPOSE: To investigate the rate of visual field and optic disc change in patients with distinct patterns of glaucomatous optic disc damage. DESIGN: Prospective longitudinal study. PARTICIPANTS: A total of 131 patients with open-angle glaucoma with focal (n = 45), diffuse (n = 42), and sclerotic (n = 44) optic disc damage. METHODS: Patients were examined every 4 months with standard automated perimetry (SAP, SITA Standard, 24-2 test, Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA) and confocal scanning laser tomography (CSLT, Heidelberg Retina Tomograph, Heidelberg Engineering GmbH, Heidelberg, Germany) for a period of 4 years. During this time, patients were treated according to a predefined protocol to achieve a target intraocular pressure (IOP). Rates of change were estimated by robust linear regression of visual field mean deviation (MD) and global optic disc neuroretinal rim area with follow-up time. MAIN OUTCOME MEASURES: Rates of change in MD and rim area. RESULTS: Rates of visual field change in patients with focal optic disc damage (mean -0.34, standard deviation [SD] 0.69 dB/year) were faster than in patients with sclerotic (mean -0.14, SD 0.77 dB/year) and diffuse (mean +0.01, SD 0.37 dB/year) optic disc damage (P = 0.003, Kruskal-Wallis). Rates of optic disc change in patients with focal optic disc damage (mean -11.70, SD 25.5 ×10(-3) mm(2)/year) were faster than in patients with diffuse (mean -9.16, SD 14.9 ×10(-3) mm(2)/year) and sclerotic (mean -0.45, SD 20.6 ×10(-3) mm(2)/year) optic disc damage, although the differences were not statistically significant (P = 0.11). Absolute IOP reduction from untreated levels was similar among the groups (P = 0.59). CONCLUSIONS: Patients with focal optic disc damage had faster rates of visual field change and a tendency toward faster rates of optic disc deterioration when compared with patients with diffuse and sclerotic optic disc damage, despite similar IOP reductions during follow-up.


Subject(s)
Glaucoma, Open-Angle/physiopathology , Optic Disk/pathology , Optic Nerve Diseases/physiopathology , Vision Disorders/physiopathology , Visual Fields/physiology , Aged , Female , Humans , Intraocular Pressure/physiology , Longitudinal Studies , Male , Microscopy, Confocal , Middle Aged , Prospective Studies , Tonometry, Ocular , Visual Field Tests
10.
Dev Genes Evol ; 216(1): 1-9, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16208536

ABSTRACT

The mechanical loading of striated muscle is thought to play an important role in shaping bones and joints. Here, we examine skeletogenesis in late embryogenesis (embryonic day 18.5) in Myf5-/-:MyoD-/- fetuses completely lacking striated muscle. The phenotype includes enlarged and fused cervical vertebrae and postural anomalies, some viscerocranial anomalies, long bone truncation and fusion, absent deltoid tuberosity of the humerus, scapular and clavicular hypoplasia, cleft palate, and cleft sternum. In contrast, neurocranial bone development was essentially normal. While the magnitude of individual effects varied throughout the skeletal system, the results are consistent with skeletal development depending on functional muscles. Novel abnormalities in the amyogenic fetuses relative to less severely paralyzed phenotypes extend our understanding of skeletogenic dependence on embryonic muscle contraction and static loading.


Subject(s)
Bone and Bones/embryology , Muscle Contraction/genetics , Muscle, Skeletal/embryology , MyoD Protein/genetics , Myogenic Regulatory Factor 5/genetics , Osteogenesis/genetics , Animals , Bone and Bones/abnormalities , Fetus , Mice , Mice, Knockout , Muscle, Skeletal/physiology , MyoD Protein/physiology , Myogenic Regulatory Factor 5/deficiency , Myogenic Regulatory Factor 5/physiology
11.
Int J Dev Neurosci ; 23(7): 613-20, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16183241

ABSTRACT

The aim of this study was to approach the question of neuronal dependence on neurotrophins during embryonic development in mice in a way other than gene targeting. We employed amyogenic mouse embryos and fetuses that develop without any skeletal myoblasts or skeletal muscle and consequently lose motor and proprioceptive neurons. We hypothesized that if, in spite of the complete inability to maintain motor and proprioceptive neurons, the remaining spinal and dorsal root ganglia tissues of amyogenic fetuses still contain any of the neurotrophins, that particular neurotrophin alone is not sufficient for the maintenance of motor and proprioceptive neurons. Moreover, if the remaining spinal and dorsal root ganglia tissues still contain any of the neurotrophins, that particular neurotrophin alone may be sufficient for the maintenance of the remaining neurons (i.e., mostly non-muscle- and a few muscle-innervating neurons). To test the role of the spinal cord and dorsal root ganglia tissues in the maintenance of its neurons, we performed immunohistochemistry employing double-mutant and control tissues and antibodies against neurotrophins and their receptors. Our data suggested that: (a) during the peak of motor neuron cell death, the spinal cord and dorsal root ganglia distribution of neurotrophins was not altered; (b) the distribution of BDNF, NT-4/5, TrkB and TrkC, and not NT-3, was necessary for the maintenance of the spinal cord motor neurons; (c) the distribution of BDNF, NT-4/5 and TrkC, and not NT-3 and Trk B, was necessary for the maintenance of the DRG proprioceptive neurons; (d) NT-3 was responsible for the maintenance of the remaining neurons and glia in the spinal cord and dorsal root ganglia (possibly via TrkB).


Subject(s)
Ganglia, Spinal/cytology , Ganglia, Spinal/physiology , Motor Neurons/physiology , Nerve Growth Factors/physiology , Neurons, Afferent/physiology , Proprioception/physiology , Spinal Cord/cytology , Spinal Cord/physiology , Animals , Brain-Derived Neurotrophic Factor/metabolism , Cell Death , Female , Ganglia, Spinal/embryology , Immunohistochemistry , Mice , Mice, Knockout , MyoD Protein/genetics , MyoD Protein/physiology , Myogenic Regulatory Factor 5/genetics , Myogenic Regulatory Factor 5/physiology , Nerve Growth Factors/genetics , Pregnancy , Receptor, trkB/genetics , Receptor, trkB/metabolism , Receptor, trkC/genetics , Receptor, trkC/metabolism , Receptors, Nerve Growth Factor/metabolism , Spinal Cord/embryology
12.
Dev Dyn ; 234(3): 659-69, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16193506

ABSTRACT

To determine which combination of skeletal muscle-derived neurotrophic factors may be important for the survival of specific subpopulations of developing spinal cord motor neurons, we used Myf5 and MyoD (myogenic regulatory factors) knockouts, containing differentially committed myogenic precursor cells (MPCc) and immunohistochemistry against several muscle-secreted neurotrophic factors. At the peak of motor neuron cell death, skeletal muscle development is delayed in the back and body wall muscles of Myf5-/- embryos and in the limb muscles of MyoD-/- embryos. We hypothesized that, if the skeletal muscle was indeed an important source of survival factors for motor neurons, the back, the abdominal wall, and the forelimb MPCs of Myf5-/- or MyoD-/- embryos should produce at least some neurotrophic factors necessary for the survival of motor neurons. In this report, we demonstrate that (1) different MPCs lacking Myf5, MyoD, or Myf5/MyoD have different capabilities in providing factors potentially required for the survival of motor neurons and intramuscular nerve branching, (2) MPCs in double-mutant embryos do not contain neurotrophic factors in the absence of myogenic specification, and (3) different subpopulations of MPCs contain different combinations of neurotrophic factors potentially required for the survival of the specific subpopulations of innervating motor neurons.


Subject(s)
Motor Neurons/cytology , Motor Neurons/metabolism , Muscle, Skeletal/metabolism , Nerve Growth Factors/metabolism , Spinal Cord/cytology , Animals , Apoptosis , Cell Survival , Gene Expression Regulation , Mice , Mice, Knockout , Muscle, Skeletal/cytology , Muscle, Skeletal/embryology , Mutation/genetics , MyoD Protein/genetics , MyoD Protein/metabolism , Myogenic Regulatory Factor 5/deficiency , Myogenic Regulatory Factor 5/genetics , Myogenic Regulatory Factor 5/metabolism , Nerve Growth Factors/genetics
13.
Dev Biol ; 261(2): 324-36, 2003 Sep 15.
Article in English | MEDLINE | ID: mdl-14499644

ABSTRACT

To further investigate the role of MyoD during skeletal myogenesis, we backcrossed mdx mutant mice (lacking dystrophin) with MyoD knock-out mice to obtain viable mice with MyoD allele on a pure mdx background. However, after nine generations of backcrossing, it was not possible to obtain a viable mdx:MyoD-/- phenotype (designated as: mdx:MyoD-/-(9th)). The compound-mutant embryos were examined just before birth. Essentially normal Myf5-dependent and most of the MyoD-dependent musculature was observed. By contrast, the skeletal muscle compartment of the diaphragm was significantly reduced. The mesenchymal compartment of the diaphragm was intact and no herniations were observed. Other examined organs (e.g., liver, kidney, brain, etc.) showed no histological abnormalities. Pulmonary hypoplasia was determined as the cause of neonatal death. Therefore, using a different approach, our new data supplement our previous findings and suggest an essential role for MyoD in development of skeletal muscle of the diaphragm. The failure of mdx:MyoD-/-(9th) diaphragm to develop normally is not caused by a reduced number of satellite cells, but from the inability of stem cells to progress through the myogenic program. Our data also suggest that functions of MyoD and Myf5 (and the respective muscle precursor cell sub-populations) are not entirely redundant by term, as previously suggested, since Myf5 is not capable of fully substituting for MyoD in the diaphragm development.


Subject(s)
DNA-Binding Proteins , Diaphragm/embryology , Genes, Lethal , MyoD Protein/genetics , Trans-Activators , Animals , Dystrophin/genetics , Dystrophin/metabolism , Extremities/embryology , Mice , Mice, Inbred mdx , Muscle Development/physiology , Muscle Proteins/metabolism , Muscle, Skeletal/embryology , MyoD Protein/metabolism , Myogenic Regulatory Factor 5
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