ABSTRACT
Community engagement (CE) is praised to be a powerful vehicle in empowering communities with knowledge and skills to make informed decisions for better health care. Several CE approaches have been proposed to improve participants' and research communities' understanding of genomic research including pharmacogenomic information and results. However, there is limited literature on how these approaches can be used to communicate findings of pharmacogenomic research to communities of people living with HIV. This study explored stakeholders' perspectives on the role of community engagement in promoting understanding of pharmacogenomic research results among people living with HIV. We adopted a qualitative approach that involved 54 stakeholders between September 2021 and February 2022. We held five focus group discussions among 30 community representatives from five research institutions, 12 key informant interviews among researchers, and 12 in-depth interviews among ethics committee members. A thematic approach was used to analyze the results. Five themes merged from this data and these included (i) benefits of engaging communities prior to returning individual pharmacogenomic research results to participants. (ii) Obtaining community consensus on the kinds of pharmacogenomic results to be returned. (iii) Opinions on how pharmacogenomic research information and results should be communicated at community and individual levels. (iv) Perceived roles of community stakeholders in promoting participants' understanding and utilization of pharmacogenomic research results. (v) Perceived challenges of engaging communities when returning individual results to research participants. Stakeholders opined that CE facilitates co-learning between researchers and research communities. Researchers can adapt existing CE approaches that are culturally acceptable for meaningful engagement with minimal ethical and social risks when communicating pharmacogenomic research results. CE approaches can facilitate understanding of pharmacogenomic research and findings among research participants and communities. Therefore, if creatively adapted, existing and new CE approaches can enable researchers to communicate simple and understandable results of pharmacogenomic research.
Subject(s)
Acquired Immunodeficiency Syndrome , Humans , Pharmacogenetics , Focus Groups , Delivery of Health Care , Research PersonnelABSTRACT
Background: Low back pain is the leading global cause of years lost to disability. The study aimed to assess the health-related quality of life in patients with low back pain attending an outpatient clinic at a national referral hospital in Uganda. Methods: This was a hospital based cross-sectional study that involved 250 adult patients with low back pain. Data were collected using the modified short form-36 Health Survey questionnaire. Data were summarised using descriptive statistics. Analysis of Variance, the F-test and linear regression analysis were used for inferential statistics. Result: Majority of participants were female (66.4%) with a mean age of 60 years (SD 12.9, range 20- 87) and 44.6% were manual labourers. 70% of participants had had low back pain for more than one year and 74% had neuropathic symptoms. The total quality of life of participants was poor with a mean score of 31.9 (SD 15.6). The factors that significantly influenced quality of life included performing manual work (p=0.01), being unemployed (p=0.027) and weakness in the lower limbs (p=0.01). Conclusion: Patients with low back pain had a poor quality of life that was significantly influenced by being unemployed, doing manual work and clinical features of nerve compression.
Subject(s)
Low Back Pain , Quality of Life , Adult , Humans , Male , Female , Middle Aged , Cross-Sectional Studies , Tertiary Care Centers , Low Back Pain/epidemiology , Uganda/epidemiology , Surveys and QuestionnairesABSTRACT
Background: The increasing numbers of students studying human anatomy at Makerere University are beginning to overwhelm available resources, which presents challenges in learning and necessitates an evaluation of alternative ways to enhance anatomy learning.The increasing numbers of students overwhelm resources available and presents challenges in learning. This necessitates an evaluation of alternatives to enhance gross anatomy learning at Makerere University College of Health Sciences. The study aimed to assess the usage of visual aids and generate necessary information to enhance learning. Methods: A cross-sectional study employing a concurrent triangulation mixed method design was conducted among 44 graduate students actively participating in cadaveric dissection. Data was collected using self-administered questionnaires and two focus group discussions. Descriptive statistics and thematic analysis were used to summarize data. Results: Most participants were male (77.3%) with a mean age of 31.5 years (SD 3.9, Range, 27-45 years). A majority of graduate students reported using non-traditional methods (online sources) to supplement learning. Students commonly used hard copies of Cunningham Manual of Practical Anatomy (88.6%) supplemented with well-illustrated textbooks (79.5%) and online dissection videos (72.7%). Students expressed most satisfaction with the use of videos and well-illustrated text books in supplementing learning. The availability of these electronic resources was limited by factors such as poor internet connectivity and the need to pay for online licenses and subscription fees. Conclusion: Graduate students in the Department of Anatomy at MakCHS are using non-traditional methods to supplement their learning. However, there are several challenges to accessing digital resources. There is a need to support students with accessing visual aids through integrating newer teaching modalities and modern technology to promote interest and retention of anatomical knowledge.
Subject(s)
Anatomy , Education, Medical, Undergraduate , Students, Medical , Male , Humans , Adult , Female , Universities , Cross-Sectional Studies , Students , Attitude , Curriculum , Audiovisual Aids , Anatomy/education , Education, Medical, Undergraduate/methods , Surveys and QuestionnairesABSTRACT
Little is known about whether people living with HIV would like to receive their results from pharmacogenomics research. This study explored the factors influencing participants' preferences and the reasons for their desire to receive individual results from pharmacogenomics research. We employed a convergent parallel mixed methods study design comprising a survey of 225 research participants and 5 deliberative focus group discussions with 30 purposively selected research participants. Almost all (98%) participants wanted to receive individual pharmacogenomics research results. Reasons for the desire to receive results were reciprocity for valuable time and effort, preparing for future eventualities, and the right to information about their health. Overall, participants desire to receive feedback from pharmacogenomics research, particularly if results are well established and clinically actionable.
Subject(s)
HIV Infections , Pharmacogenetics , Humans , Uganda , Focus Groups , Surveys and Questionnaires , HIV Infections/drug therapyABSTRACT
PURPOSE: Low-and-middle-income countries (LMICs) have a large burden of major limb loss. No recent study has reported on Uganda's state of public sector prosthetics services. This study aimed to document the landscape of major limb loss, and the structure of available prosthetics services in Uganda. METHODS: This study involved a retrospective review of medical records at Mulago National Referral Hospital, Fort Portal Regional Referral Hospital, and Mbale Regional Referral Hospital, and a cross-sectional survey of personnel involved in the fabrication and fitting of prosthetic devices across orthopaedic workshops in the country. RESULTS: Upper limb amputations accounted for 14.2%, and lower limb accounted for 81.2%. Gangrene (30.3%) was the leading cause of amputation, followed by road traffic accidents and diabetes mellitus. Orthopaedic workshops offered decentralised services, and most materials used were imported. Essential equipment was largely lacking. Orthopaedic technologists had diverse experience and skill sets, but many other factors limited their service provision. CONCLUSION: The Ugandan public healthcare system lacks adequate prosthetic services both in terms of personnel and supporting resources, including equipment, materials, and components. The provision of prosthetics rehabilitation services is limited, especially in rural regions. Decentralising services could improve patients' access to prosthetic services.Implications for RehabilitationAvailability and accessibility of prosthetic services are essential to the rehabilitation and reintegration of amputees into communities in Low-and-Middle-Income countries (LMICs).For stakeholders to formulate effective plans to address issues within prosthetics service provision, quality data on the current state of services is necessary.Service providers should prioritise the decentralisation of prosthetic rehabilitation services, especially for patients in rural areas, to improve access and reach of these services.To achieve optimal limb functionality after amputation for both lower and upper limb amputees, rehabilitation professionals working in LMICs should focus on delivering comprehensive multidisciplinary rehabilitation services.Orthopaedic personnel should ensure complete and accurate documentation of patient information following amputation to enable effective tracking and monitoring of patient care to improve outcomes of rehabilitation.
ABSTRACT
INTRODUCTION: Automated mobile phone surveys (MPS) can be used to collect public health data of various types to inform health policy and programs globally. One challenge in administering MPS is identification of an appropriate and effective participant consent process. This study investigated the impact of different survey consent approaches on participant disposition (response characteristics and understanding of the purpose of the survey) within the context of an MPS that measured noncommunicable disease (NCD) risk factors across Colombia and Uganda. METHODS: Participants were randomized to one of five consent approaches, with consent modules varying by the consent disclosure and mode of authorization. The control arm consisted of a standard consent disclosure and a combined opt-in/opt-out mode of authorization. The other four arms consist of a modified consent disclosure and one of four different forms of authorization (i.e., opt-in, opt-out, combined opt-in/opt-out, or implied). Data related to respondent disposition and respondent understanding of the survey purpose were analyzed. RESULTS: Among 1889 completed surveys in Colombia, differences in contact, response, refusal, and cooperation rates by study arms were found. About 68% of respondents correctly identified the survey purpose, with no significant difference by study arm. Participants reporting higher levels of education and urban residency were more likely to identify the purpose correctly. Participants were also more likely to accurately identify the survey purpose after completing several survey modules, compared to immediately following the consent disclosure (78.8% vs 54.2% correct, p<0.001). In Uganda, 1890 completed surveys were collected. Though there were differences in contact, refusal, and cooperation rates by study arm, response rates were similar across arms. About 37% of respondents identified the survey purpose correctly, with no difference by arm. Those with higher levels of education and who completed the survey in English were able to more accurately identify the survey purpose. Again, participants were more likely to accurately identify the purpose of the survey after completing several NCD modules, compared to immediately following the consent module (42.0% vs 32.2% correct, p = 0.013). CONCLUSION: This study contributes to the limited available evidence regarding consent procedures for automated MPS. Future studies should develop and trial additional interventions to enhance consent for automated public health surveys, and measure other dimensions of participant engagement and understanding.
Subject(s)
Cell Phone , Noncommunicable Diseases , Humans , Uganda , Colombia , Surveys and Questionnaires , Risk Factors , Informed ConsentABSTRACT
Research is crucial to progress in nephrology. It is important that studies are conducted rigorously from the scientific perspective, as well as in adherence to ethical standards. Traditional clinical research places a high value on individual research subject autonomy. Research questions often include the clinical effectiveness of new interventions studied under highly controlled conditions. Such research has brought the promise of new game-changers in nephrology, such as the sodium-glucose cotransporter 2 inhibitors. Implementation research takes such knowledge further and investigates how to translate it into broader-scale policy and practice, to achieve swift and global uptake, with a focus on justice and equity. Newer challenges arising globally in research ethics include those relating to oversight of innovation, biobanking and big data, human-challenge studies, and research during emergencies. This article details the history of clinical research ethics and the role of research ethics committees, describes the evolving spectrum of biomedical research in human medicine, and presents emerging clinical research ethics issues using illustrative examples and a hypothetical case study. It is imperative that researchers and research ethics committees are well versed in the ethical principles of all forms of human research such that research is conducted to the highest standards and that effective interventions can be implemented at scale as rapidly as possible.
Subject(s)
Biomedical Research , Nephrology , Biological Specimen Banks , Ethics Committees, Research , Ethics, Research , HumansABSTRACT
Sub-Saharan Africa has the worst global shortage of health professionals. The use of eLearning interventions, that lead to increased interactions according to the Interaction Equivalency theorem, is a potential means of addressing this shortage of health professionals. In this audit we set out to determine the effect of an eLearning general histology and general embryology intervention on student's summative examination scores. The audit compared the written and practical summative examination scores of three sets of student examinations one of which had a five-week eLearning intervention. Two of the examinations were for the same students in one year but different courses while the other two were for students doing the same subject but in different years. In each of the above pair of examinations there was one group from the course that had the eLearning intervention. A Bayesian multilevel regression modelling approach was used to analyse the student scores. The course with the online eLearning intervention had significantly better scores (p-value < 0.01), than the course on a different subject offered at the same time to the same students without the intervention and the same course with students from the previous academic year. On controlling for other factors, the eLearning intervention led to higher examination scores though this was not significant. Student's nationality, sponsorship and program significantly affected the examination scores, controlling for other factors. Overall the students in the course with the online eLearning intervention had significantly better examination scores. The student's nationality, sponsorship and program significantly affect their examination scores. Future, larger and or qualitative studies, are needed to further explore the effect of these factors on student's examination scores.
ABSTRACT
INTRODUCTION: Research integrity is the foundation of credible research and a pre-requisite for a successful academic research environment. Lately, a lot of revelations of fraud and other unacceptable behaviour in research have been highly publicized in scientific journals and mass media. Whereas institutions in developed countries have developed guidelines and regulations to ensure responsible conduct of research and appropriately deal with cases of research misconduct, low- and middle-income countries seem to be lagging behind. In Uganda, there seems to be lack of coordinated efforts to address the problem of research misconduct both at the national and institutional level. OBJECTIVE: To propose a framework for fostering scientific integrity and deterring misconduct in research in Ugandan research and academic institutions. METHODS: A review of literature on scientific integrity, scientific misconduct, responsible conduct of research, and international ethical guidelines was done. RESULTS: Basing on the 2012 Inter-Academy Council policy report, initiatives to promote responsible conduct of research in Ugandan research and academic institutions are proposed. CONCLUSION: With the proposed framework, an honest and trustworthy research enterprise in Uganda based on principles of scientific integrity is envisioned.
Subject(s)
Biomedical Research/standards , Biomedical Research/education , Clinical Trials as Topic/standards , Developing Countries , Ethics, Research , Humans , Registries , Research Support as Topic , Scientific Misconduct , UgandaABSTRACT
BACKGROUND: Effective utilization of computers and their applications in medical education and research is of paramount importance to students. The objective of this study was to determine the association between owning a computer and use of computers for research data analysis and the other factors influencing health professions students' computer use for data analysis. METHODS: We conducted a cross sectional study among undergraduate health professions students at three public universities in Uganda using a self-administered questionnaire. The questionnaire was composed of questions on participant demographics, students' participation in research, computer ownership, and use of computers for data analysis. Descriptive and inferential statistics (uni-variable and multi- level logistic regression analysis) were used to analyse data. The level of significance was set at 0.05. RESULTS: Six hundred (600) of 668 questionnaires were completed and returned (response rate 89.8%). A majority of respondents were male (68.8%) and 75.3% reported owning computers. Overall, 63.7% of respondents reported that they had ever done computer based data analysis. The following factors were significant predictors of having ever done computer based data analysis: ownership of a computer (adj. OR 1.80, p = 0.02), recently completed course in statistics (Adj. OR 1.48, p =0.04), and participation in research (Adj. OR 2.64, p <0.01). CONCLUSIONS: Owning a computer, participation in research and undertaking courses in research methods influence undergraduate students' use of computers for research data analysis. Students are increasingly participating in research, and thus need to have competencies for the successful conduct of research. Medical training institutions should encourage both curricular and extra-curricular efforts to enhance research capacity in line with the modern theories of adult learning.
Subject(s)
Computers/statistics & numerical data , Health Personnel/statistics & numerical data , Schools, Medical/statistics & numerical data , Statistics as Topic , Students, Medical/statistics & numerical data , Female , Humans , Logistic Models , Male , Uganda , UniversitiesABSTRACT
BACKGROUND: Though seen as a convenient method of carrying books and other scholastic materials including food items, schoolbags are believed to contribute to back and other musculoskeletal problems in school going children. This study set out to determine the prevalence of low back and other musculoskeletal pains and describe their relationship with schoolbag use in pupils. RESULTS: This was a cross-sectional descriptive study involving 532 pupils from six primary schools with a mean age of 13.6 years. Analyses included the chi- square test, independent t tests, regression analysis and test for trend across ordered groups. Backpacks were the most common type of schoolbag and younger children carried disproportionately heavier bags. Urban pupils were younger, carried significantly heavier bags, and less likely to complain about schoolbag weight than the rural pupils. About 30.8% of the pupils carried schoolbags which were more than 10% of their body weight. About 88.2% of pupils reported having body pain especially in the neck, shoulders and upper back. About 35.4% of the children reported that carrying the schoolbag was the cause of their musculoskeletal pain. The prevalence of lower back pain was 37.8%. There was significant association between low back pain and; method of bag carriage (p < 0.0001), long duration of walking (odds ratio 2.67, 95% CI 1.38- 5.16) and the time spent sitting after school (p = 0.02). Only 19% had lockers at school. CONCLUSION: Urban pupils were younger, carried significantly heavier bags, and less likely to complain about schoolbag weight than the rural pupils. The majority of pupils complained of musculoskeletal pain of which 35.4% was attributed to the schoolbags.The prevalence of lower back pain was 37.8%. Schools need to provide lockers and functional libraries in order to avoid excessive loading and repetitive strain injuries.
Subject(s)
Musculoskeletal Pain/epidemiology , Students , Adolescent , Back/physiopathology , Body Weight , Child , Female , Humans , Male , Musculoskeletal Pain/physiopathology , Prevalence , Rural Population , Schools , Shoulder/physiopathology , Surveys and Questionnaires , Uganda/epidemiology , Urban Population , Weight-Bearing , Young AdultABSTRACT
BACKGROUND: Musculoskeletal disorders (MSD) constitute one of the main occupational hazards among health care workers. However, few epidemiological studies on work related MSD among nursing professionals have been carried out in Africa. The purpose of this study was to assess the work related musculoskeletal disorders and associated risk factors among nursing professionals in Uganda. METHODS: This was a cross-sectional study of MSD among 880 nursing professionals from five selected hospitals in Uganda. Data was collected using a questionnaire adapted from the Dutch Musculoskeletal and Nordic Musculoskeletal questionnaires. Descriptive (mean, standard deviation and percentages) and inferential (Chi square test and logistic regression analysis) statistics were used to analyse data. Alpha level was set at p < 0.05. RESULTS: A total of 741 completed questionnaires were analysed (response rate 85.4%). The average age of the respondents was 35.4 (SD 10.7) years and a majority were female (85.7%). The average working hours per week was 43.7 (SD 18.9 hours). The 12-month period-prevalence of MSD at anybody site was 80.8%. The most common site of MSD was the lower back (61.9%). Significant risk factors for reported MSD included often working in a slightly bent posture (adjOR 2.25, 95% CI 1.20-4.26), often working in a slightly twisted posture for long (adjOR 1.97, 95% CI 1.03-3.77), mental exhaustion (adjOR 2.05, 95% CI 1.17-3.5), being absent from the work station for more than 6 months due to illness or an accident (adjO|R, 4.35, 95% CI 1.44-13.08) and feeling rested after a break (adjOR 2.09, 95% CI 1.16-3.76). CONCLUSIONS: Musculoskeletal disorders affect more than 80% of nursing professionals in Uganda with the most commonly, affected site being the lower back. Significant risk factors for MSD include; being absent from the work station for more than 6 months due to illness or an accident, working in awkward postures, pushing/pulling of heavy loads and mental exhaustion. There is a need for greater advocacy, better working conditions and adoption of strategies to reduce occupational injuries.
ABSTRACT
Using a nonlinear three-dimensional finite element analysis simulating loading conditions, we designed a new type of proximal-fitting, anterolaterally-flared, arc-deposit hydroxyapatite-coated anatomical femoral stem (FMS-anatomic stem; Japan Medical Materials, Osaka, Japan) for cementless total hip arthroplasty (THA) for Japanese patients with dysplastic hip osteoarthritis. The aim of the present study was to analyze the clinical and radiographic outcomes of the new stem. We reviewed 143 consecutive patients (164 hips; 13 men, 14 hips; 130 women, 150 hips; age at surgery, 56.6 +/- 7.6 years, mean +/- SD, range, 30-74) who underwent cementless THA using the FMS-anatomic stem at a single institution, with a follow-up period of 7.6 +/- 1.6 years (range, 5.3-11.0). Harris Hip score improved from 46.1 +/- 12.6 before surgery to 90.0 +/- 8.9 points post-THA. The 7.6-year survival rate of the stem was 99.0% after revision for aseptic loosening. Radiographs at follow-up confirmed the stability of the femoral stems within the femoral canal in all cases, with sufficient bone ingrowth. None of the patients had subsidence of the stem exceeding 2.0 mm within the femoral canal or changes in varus or valgus position of more than 2.0 degrees . The FMS-anatomic stem provided excellent results in patients with dysplastic hip osteoarthritis. Our analysis confirmed reduced radiolucency around the stem in Gruen zones, minimal subsidence, appropriate stress shielding, and promising medium-term stability within the femoral canal in our patients.
Subject(s)
Arthroplasty, Replacement, Hip/methods , Femur/diagnostic imaging , Hip Joint/diagnostic imaging , Hip Prosthesis , Osteoarthritis, Hip/surgery , Adult , Aged , Female , Femur/surgery , Follow-Up Studies , Hip Joint/surgery , Humans , Male , Middle Aged , Osteoarthritis, Hip/diagnostic imaging , RadiographyABSTRACT
Entrapment neuropathy is a frequent clinical problem that can be caused by, among other factors, mechanical compression; however, exactly how a compressive force affects the peripheral nerves remains poorly understood. In this study, using a rabbit model of sciatic nerve injury (n=12), we evaluated the time-course of changes in intraneural blood flow, compound nerve action potentials, and functioning of the blood-nerve barrier during graded mechanical compression. Nerve injury was applied using a compressor equipped with a custom-made pressure transducer. Cessation of intraneural blood flow was noted at a mean compressive force of 0.457+/-0.022 N (+/-SEM), and the compound action potential became zero at 0.486+/-0.031 N. Marked extravasation of Evans blue albumin was noted after 20 min of intraneural ischemia. The functional changes induced by compression are likely due to intraneural edema, which could subsequently result in impairment of nerve function. These changes may be critical factors in the development of symptoms associated with nerve compression.
Subject(s)
Nerve Compression Syndromes/physiopathology , Sciatic Nerve/blood supply , Action Potentials/physiology , Animals , Blood-Nerve Barrier/physiopathology , Electrophysiology , Microscopy, Fluorescence , Rabbits , Regional Blood Flow/physiology , Sciatic Nerve/physiopathology , Stress, MechanicalABSTRACT
INTRODUCTION: The aim of this study was to review the patients with lumbar epidural abscess in terms of neurological morbidity, therapeutic outcome, and prognosis, while assessing the usefulness of a new MRI staging classification and specific imaging findings as indicators for surgical management. MATERIALS AND METHODS: We reviewed 37 patients who sustained epidural abscess associated with pyogenic spondylodiscitis of the lumbar spine. Ten patients were treated conservatively, while 27 required urgent or elective surgical drainage. We studied patients with respect to symptomatology, Frankel-American Spinal Injury Association (ASIA) scale evaluation and a new proposed system of MRI staging of pyogenic spondylodiscitis (stages IV). RESULTS: Of the 37 patients with stage IV and V MRI lesions, 13 (35%) had septicemia and 8 (22%) presented with Frankel-ASIA scale C-D neurological status. All cases with ringlike enhancement on gadolinium-enhanced MRI in the epidural abscess lesions were treated surgically. Progression of local kyphosis and loss of intervertebral disk height were significantly prevented in the surgical group (P < 0.05). Improvements of neurological status and laboratory data were better in the surgical group than the conservative group (P < 0.05), with significantly short hospital stay (P < 0.05). DISCUSSION: Epidural abscess associated with pyogenic spondylodiscitis presents with various neurological symptoms. In addition to assessment of progression by clinical symptomatology, modified neurological Frankel-ASIA scaling and the currently proposed MRI staging regimen may help to consider the timing of surgical intervention. In the acute, subacute or acute-on-chronic phase and the ringlike enhancement pattern of epidural abscess on gadolinium-enhanced MRI may be an indicator for surgery.
Subject(s)
Discitis/diagnosis , Discitis/therapy , Epidural Abscess/diagnosis , Epidural Abscess/therapy , Lumbar Vertebrae/pathology , Magnetic Resonance Imaging , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Combined Modality Therapy , Contrast Media , Female , Gadolinium , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Statistics, Nonparametric , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
STUDY DESIGN.: To examine the distribution of apoptotic cells and expression of tumor necrosis factor (TNF)-alpha and its receptors in the spinal hyperostotic mouse (twy/twy) with chronic cord compression using immunohistochemical methods. OBJECTIVE.: To study the mechanisms of apoptosis, particularly in oligodendrocytes, which could contribute to degenerative change and demyelination in chronic mechanical cord compression. SUMMARY OF BACKGROUND DATA.: TNF-alpha acts as an external signal initiating apoptosis in neurons and oligodendrocytes after spinal cord injury. Chronic spinal cord compression caused neuronal loss, myelin destruction, and axonal degeneration. However, the biologic mechanisms of apoptosis in chronically compressed spinal cord remain unclear. METHODS.: The cervical spinal cord of 34 twy mice aged 20 to 24 weeks and 11 control animals were examined. The apoptotic cells were detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) staining. The expression and the localization of TNF-alpha, TNF receptor 1 (TNFR1), and TNF receptor 2 (TNFR2) were examined using immunoblot and immnohistochemical analysis. RESULTS.: The number of TUNEL-positive cells in the white matter increased with the severity of compression, which was further increased bilaterally in the white matter of twy/twy mice. Double immunofluorescence staining showed that the number of cells positive for TUNEL and RIP, a marker of oligodendrocytes, increased in the white matter with increased severity of cord compression. Immunoblot analysis demonstrated overexpression of TNF-alpha, TNFR1, and TNFR2 in severe compression. The expression of TNF-alpha appeared in local cells including microglia while that of TNFR1 and TNFR2 was noted in apoptotic oligodendrocytes. CONCLUSION.: Our results suggested that the proportion of apoptotic oligodendrocytes, causing spongy axonal degeneration and demyelination, correlated with the magnitude of cord compression and that overexpression of TNF-alpha, TNFR1, and TNFR2 seems to participate in apoptosis of such cells in the chronically compressed spinal cord.
Subject(s)
Apoptosis/physiology , Hyperostosis/metabolism , Oligodendroglia/metabolism , Receptors, Tumor Necrosis Factor, Type II/metabolism , Receptors, Tumor Necrosis Factor, Type I/metabolism , Spinal Cord Compression/metabolism , Spinal Cord/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Blotting, Western , Cell Count , Cervical Vertebrae/injuries , Cervical Vertebrae/metabolism , Cervical Vertebrae/pathology , Chronic Disease , Fluorescent Antibody Technique , Hyperostosis/pathology , In Situ Nick-End Labeling , Mice , Mice, Transgenic , Microscopy, Electron, Transmission , Microscopy, Fluorescence , Nerve Degeneration/metabolism , Nerve Degeneration/pathology , Neurons/metabolism , Neurons/pathology , Oligodendroglia/pathology , Severity of Illness Index , Spinal Cord/pathology , Spinal Cord Compression/pathology , Statistics, Nonparametric , Stress, MechanicalABSTRACT
OBJECT: The effects of sagittal kyphotic deformities or mechanical stress on the development of cervical spondylotic myelopathy, or the reduction and fusion of kyphotic sagittal alignment have not been consistently documented. The aim in this study was to determine the effects of kyphotic sagittal alignment of the cervical spine in terms of neurological morbidity and outcome after 2 types of surgical intervention. METHODS: The authors retrospectively reviewed the records of 476 patients who underwent cervical spine surgeries for spondylotic myelopathy between 1993 and 2006 at their university medical center. Among these were identified 43 patients-30 men and 13 women, with a mean age of 58.8 years-who had cervical kyphosis exceeding 10 degrees on preoperative sagittal lateral radiographs obtained in the neutral position, and their cases were analyzed in this study. Anterior decompression with interbody fusion was conducted in 28 patients, and en bloc open-door C3-7 laminoplasty in 15 patients. Both pre- and postoperative neurological, radiographic, and MR imaging findings were assessed in both surgical groups. RESULTS: The mean preoperative kyphotic angle in all 43 patients was 15.9 +/- 5.9 degrees in the neutral position. Segmental instability was noted in 26 patients (61%) and reversed dynamic spinal canal stenosis at the level above the local kyphosis in 22 (51%). Preoperative T2-weighted MR images showed high-intensity signal within the cord at and around the level of maximal compression or segmental instability in 28 patients (65%). The mean kyphotic angle in both the neutral and flexion positions was significantly smaller at 4-6 weeks after surgery in the anterior spondylectomy group than in the laminoplasty group (p < 0.001). Furthermore, the angle in the neutral position was significantly smaller on follow-up in the anterior spondylectomy group than in the laminoplasty group (p = 0.034). The transverse area of the spinal cord was significantly larger in the anterior spondylectomy group than in the laminoplasty group on follow-up (p = 0.037). Preoperative neurological scores (assessed using the Japanese Orthopaedic Association scale) and improvement on follow-up > or = 2 years after treatment (average 3.3 years) were not significantly different between the 2 groups; however, there was a significant difference in Japanese Orthopaedic Association score at 4-6 weeks postoperatively (p = 0.047). CONCLUSIONS: Kyphotic deformity and mechanical stress in the cervical spine may play an important role in neurological dysfunction. In a select group of patients with kyphotic deformity > or = 10 degrees , adequate correction of local sagittal alignment may help to maximize the chance of neurological improvement.
Subject(s)
Cervical Vertebrae/surgery , Decompression, Surgical/methods , Kyphosis/surgery , Neurosurgical Procedures/methods , Spondylosis/surgery , Aged , Cervical Vertebrae/diagnostic imaging , Female , Follow-Up Studies , Humans , Kyphosis/diagnostic imaging , Kyphosis/physiopathology , Laminectomy/methods , Male , Middle Aged , Radiography , Retrospective Studies , Spondylosis/diagnostic imaging , Spondylosis/physiopathology , Stress, Mechanical , Treatment OutcomeABSTRACT
We describe a 76-year-old woman who presented with painful muscle weakness and numbness in both legs secondary to grossly ossified meningiomas at the T8 and T11-T12 vertebral levels. Midline durotomy followed by en bloc excision of the tumours, together with partial resection of the dura mater and the arachnoid, was performed. Histopathological examination showed both tumours consisted of three different histological patterns: psammomatous, fibrous, and metaplastic subtypes. Immunostaining for bone morphogenetic protein-2 and vascular endothelial growth factor was significantly positive in the areas surrounding mature bone tissues in the metaplastic and psammomatous subtypes.
Subject(s)
Meningeal Neoplasms/metabolism , Meningioma/metabolism , Ossification, Heterotopic/metabolism , Aged , Bone Morphogenetic Protein 2/metabolism , Female , Humans , Magnetic Resonance Imaging/methods , Meningeal Neoplasms/complications , Meningioma/complications , Mucin-1/metabolism , Ossification, Heterotopic/etiology , Thoracic Vertebrae/pathology , Vascular Endothelial Growth Factor A/metabolism , Vimentin/metabolismABSTRACT
OBJECT: The aims of this study were to review the clinicoradiological findings in patients who underwent decompressive surgery for proximal and distal types of muscle atrophy caused by cervical spondylosis and to discuss the outcome and techniques of surgical intervention. METHODS: Fifty-one patients (43 men and 8 women) with proximal (37, with arm drop) and distal muscle atrophy (14, with wrist drop) underwent cervical decompression (39 anterior decompressions and 12 open-door C3-7 laminoplasties with microsurgical foraminotomy) for muscle weakness in the upper extremities. The clinical course, type of spinal cord compression, abnormal signal intensity on high-resolution MR imaging, and postdecompression improvement in muscle power were reviewed at a mean follow-up of 2.6 years (range 0.8-9.4 years). RESULTS: The most commonly affected vertebrae were C4-5 and C5-6, and C5-6 and C6-7 in patients with proximal or distal muscle atrophy, respectively; the respective numbers of affected vertebrae were 1.5 and 2.2. Transaxial MR imaging showed medial compression of the spinal cord in 20 patients (in 12 with proximal and 8 with distal muscle atrophy), paramedial compression in 22 (17 and 5 patients, respectively), and foraminal compression in 9 (8 and 1 patient, respectively). Increased signal intensity on MR imaging was observed in 85.0, 22.7, and 11.1% of cases of medial, paramedial, and foraminal compression, respectively. Increased signal intensity at the affected muscle segment level was observed in 52.9, 40.0, and 0% of cases, respectively. Sixty-two percent of patients with proximal muscle atrophy gained 1 or more grades of muscle power on manual muscle testing (MMT), whereas 64.3% with distal muscle atrophy failed to gain even 1 grade of improvement. The recovery of muscle power correlated with disease duration and the percent voltage of Erb point or wrist-stimulated muscle evoked potentials but not with preoperative MMT, longitudinal range of spinal cord compression, signal change on T2-weighted MR imaging, or surgical procedure. CONCLUSIONS: Surgical outcome in patients with distal muscle atrophy was inferior to that in patients with proximal atrophy. The distal type was characterized by a long preoperative period, a greater number of cervical spine misalignments, a narrow spinal canal, and increased signal intensity on T2-weighted MR imaging. It is essential to perform a careful neurological evaluation, including sensory examination of the lower limbs, as well as neuroradiological and neurophysiological assessments to avoid confusion with motor neuron disease and to detect the coexistence of amyotrophic lateral sclerosis, especially when surgical treatment of cervical spondylosis is planned. The results of careful physical examination, MR imaging studies, and electromyography studies should be comprehensively evaluated to ascertain the pathophysiology of the muscle atrophy. It is very important to distinguish the pathophysiology caused by nerve root impingements from anterior horn dysfunction when making decisions about treatment strategy. Surgical treatment--with or without foraminotomy--for amyotrophy in cervical spondylosis requires urgent action with regard to human neuroanatomy and neural innervation of the paralyzed muscles.