Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 429
Filtrar
1.
Endocrinology ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730175

RESUMO

Cultures of Sertoli cells isolated from 20-day-old mice are widely used in research as substitutes for adult Sertoli cell cultures. This practice is based on the fact that Sertoli cells cease to proliferate and become mature in vivo by days 16-20 after birth. However, it is important to verify that cultured Sertoli cells derived from 20-day-old mice do not proliferate ex vivo, and have the same properties as cultured adult Sertoli cells. Herein we described an isolation/culture method of Sertoli cells from 10-week-old adult mice with >90% purity. Properties of these cultured adult Sertoli cells were then compared with those of cultured Sertoli cells derived from 20-day-old mice (also >90% purity). By cell counting, BrdU incorporation and metaphase plate detection, we demonstrated that only adult Sertoli cells did not proliferate throughout 12 culture days. In contrast, Sertoli cells derived from 20-day-old mice still proliferated until Day 10 in culture. The morphology and profiles of intracellular lipidomics and spent medium proteomics of the two cultures were also different. Cultured adult Sertoli cells were larger in size and contained higher levels of triacylglycerols, cholesteryl esters and seminolipid, and proteins in their spent medium were mainly engaged in cellular metabolism. In contrast, proteins involved in cell division, including AMH, CDC42, collagen isoforms, were at higher levels in Sertoli cell cultures derived from 20-day-old mice. Therefore, cultured Sertoli cells derived from 10-week-old mice rather than those from 20-day-old animals should be used for studies on properties of adult Sertoli cells.

2.
J Proteome Res ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31599596

RESUMO

The Human Proteome Organization's (HUPO) Human Proteome Project (HPP) developed Mass Spectrometry (MS) Data Interpretation Guidelines that have been applied since 2016. These guidelines have helped ensure that the emerging draft of the complete human proteome is highly accurate and with low numbers of false-positive protein identifications. Here, we describe an update to these guidelines based on consensus-reaching discussions with the wider HPP community over the past year. The revised 3.0 guidelines address several major and minor identified gaps. We have added guidelines for emerging data independent acquisition (DIA) MS workflows and for use of the new Universal Spectrum Identifier (USI) system being developed by the HUPO Proteomics Standards Initiative (PSI). In addition, we discuss updates to the standard HPP pipeline for collecting MS evidence for all proteins in the HPP, including refinements to minimum evidence. We present a new plan for incorporating MassIVE-KB into the HPP pipeline for the next (HPP 2020) cycle in order to obtain more comprehensive coverage of public MS data sets. The main checklist has been reorganized under headings and subitems, and related guidelines have been grouped. In sum, Version 2.1 of the HPP MS Data Interpretation Guidelines has served well, and this timely update to version 3.0 will aid the HPP as it approaches its goal of collecting and curating MS evidence of translation and expression for all predicted ∼20 000 human proteins encoded by the human genome.

3.
Hum Fertil (Camb) ; : 1-13, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642381

RESUMO

It has recently been suggested that the human sperm genome is highly unstable, which may be a reasonable explanation as to why men, even fertile men, produce defective spermatozoa. Furthermore, an unstable genome may also explain why the semen profile of the same man changes from one ejaculate to the next. As such, we took multiple ejaculates (between 3 and 6) from 7 individuals over a 6-month period and isolated sperm through density gradients. We then compared the DNA of: (i) good and poor-quality spermatozoa within the same ejaculate; and (ii) from multiple ejaculates from the same individual. Our results suggest that on a global level, DNA present within spermatozoa is actually quite stable and similar between both good and poor sperm. This is important information for the assisted reproductive community when it comes to sperm selection.

4.
J Proteome Res ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31573204

RESUMO

The proteomic analysis of human blood and blood-derived products (e.g., plasma) offers an attractive avenue to translate research progress from the laboratory into the clinic. However, due to its unique protein composition, performing proteomics assays with plasma is challenging. Plasma proteomics has regained interest due to recent technological advances, but challenges imposed by both complications inherent to studying human biology (e.g., interindividual variability) and analysis of biospecimens (e.g., sample variability), as well as technological limitations remain. As part of the Human Proteome Project (HPP), the Human Plasma Proteome Project (HPPP) brings together key aspects of the plasma proteomics pipeline. Here, we provide considerations and recommendations concerning study design, plasma collection, quality metrics, plasma processing workflows, mass spectrometry (MS) data acquisition, data processing, and bioinformatic analysis. With exciting opportunities in studying human health and disease though this plasma proteomics pipeline, a more informed analysis of human plasma will accelerate interest while enhancing possibilities for the incorporation of proteomics-scaled assays into clinical practice.

5.
Gastroenterology ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476299

RESUMO

BACKGROUND & AIMS: Stenosis is a common complication of Crohn's disease (CD) that has no effective medical therapy. Development of antifibrotic agents will require testing in randomized controlled trials. Computed tomography enterography- and magnetic resonance enterography-based technologies might be used to measure outcomes in these trials. These approaches have been validated in studies of patients with symptomatic strictures who underwent imaging evaluations followed by resection with histopathologic grading of the intestinal tissue for inflammation and/or fibrosis (the reference standard). Imaging findings have correlated with findings from quantitative or semiquantitative histologic evaluation of the degree of fibromuscular stenosis and/or inflammation on the resection specimen. However, it is not clear whether histologic findings are an accurate reference standard. We performed a systematic review of all published histologic scoring systems used to assess stenosing CD. METHODS: We performed a comprehensive search of Embase and MEDLINE of studies through March 13, 2019, that used a histologic scoring system to characterize small bowel CD and assessed inflammatory and fibrotic alterations within the same adult individual. All scores fitting the criteria were included in our analysis, independent of the presence of stricturing disease, as long as inflammation and fibrosis were evaluated separately but in the same scoring system. RESULTS: We observed substantial heterogeneity among the scoring systems, which were not derived from modern principles for evaluative index development. None had undergone formal validity or reliability testing. None of the existing indices had been constructed according to accepted methods for the development of evaluative indices. Basic knowledge regarding their operating properties were lacking. Specific indices for evaluating the important pathologic component of myofibroblast hypertrophy or hyperplasia have not been proposed. CONCLUSIONS: In a systematic review of publications, we found a lack of validated histopathologic scoring systems for assessment of fibromuscular stenosis. Data that describe the operating properties of existing cross-sectional imaging techniques for stenosing CD should be questioned. Development and validation of a histopathology index is an important research priority.

6.
ACS Appl Mater Interfaces ; 11(43): 39560-39573, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31552734

RESUMO

Recent interest in the fields of human motion monitoring, electronic skin, and human-machine interface technology demands strain sensors with high stretchability/compressibility (ε > 50%), high sensitivity (or gauge factor (GF > 100)), and long-lasting electromechanical compliance. However, current metal- and semiconductor-based strain sensors have very low (ε < 5%) stretchability or low sensitivity (GF < 2), typically sacrificing the stretchability for high sensitivity. Composite elastomer sensors are a solution where the challenge is to improve the sensitivity to GF > 100. We propose a simple, low-cost fabrication of mechanically compliant, physically robust metallic carbon nanotube (CNT)-polydimethylsiloxane (PDMS) strain sensors. The process allows the alignment of CNTs within the PDMS elastomer, permitting directional sensing. Aligning CNTs horizontally (HA-CNTs) on the substrate before embedding in the PDMS reduces the number of CNT junctions and introduces scale-like features on the CNT film perpendicular to the tensile strain direction, resulting in improved sensitivity compared to vertically-aligned CNT-(VA-CNT)-PDMS strain sensors under tension. The CNT alignment and the scale-like features modulate the electron conduction pathway, affecting the electrical sensitivity. Resulting GF values are 594 at 15% and 65 at 50% strains for HA-CNT-PDMS and 326 at 25% and 52 at 50% strains for VA-CNT-PDMS sensors. Under compression, VA-CNT-PDMS sensors show more sensitivity to small-scale deformation than HA-CNT-PDMS sensors due to the CNT orientation and the continuous morphology of the film, demonstrating that the sensing ability can be improved by aligning the CNTs in certain directions. Furthermore, mechanical robustness and electromechanical durability are tested for over 6000 cycles up to 50% tensile and compressive strains, with good frequency responses with negligible hysteresis. Finally, both types of sensors are shown to detect small-scale human motions, successfully distinguishing various human motions with reaction and recovery times of as low as 130 ms and 0.5 s, respectively.

7.
Proteomics ; 19(21-22): e1900026, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31402590

RESUMO

While metastasis is the primary cause of colorectal cancer (CRC) mortality, the molecular mechanisms underpinning it remains elusive. Metastasis is propagated through driver oncogene/suppressor gene mutations, accompanied by passenger mutations and underlying genomic instability. To understand cancer biology, a unifying framework called the "hallmarks of cancer" (HoCs) has been developed, which organizes cell biological alterations under ten key hallmarks. Underlying these HoCs, genome instability generates mutational diversity that is amplified by inflammation. Recognizing how critical cancer cell-surface proteins influence, these HoCs have been proposed to accelerate precision medicine therapeutic development. A moderate decrease (43%↓) in HCT116 cell surface urokinase plasminogen activator receptor (uPAR) expression mitigates against many HoCs driven by these cell's KRAS and PIK3CA mutational signature. Comprehensive proteomics (whole cell lysis with two membrane protein enrichments) coupled with ingenuity pathway analysis (IPA) demonstrates that uPAR negates essential pathways across the HoC spectrum, particularly those associated with metastasis, resisting cell death, and sustaining proliferation, and parallels Cancer Hallmarks Analytics Tool analysis. Decreasing uPAR predominantly alters metastasis-related and uPAR-interactome protein expression (e.g., EGFR, caveolin, vitronectin, integrin ß4). Collectively, it is demonstrated that uPAR is a lynchpin protein capable of regulating several HoC pathways in a classical CRC mutational background.

8.
J Proteome Res ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31430157

RESUMO

The Human Proteome Project (HPP) annually reports on progress made throughout the field in credibly identifying and characterizing the complete human protein parts list and making proteomics an integral part of multiomics studies in medicine and the life sciences. NeXtProt release 2019-01-11 contains 17 694 proteins with strong protein-level evidence (PE1), compliant with HPP Guidelines for Interpretation of MS Data v2.1; these represent 89% of all 19 823 neXtProt predicted coding genes (all PE1,2,3,4 proteins), up from 17 470 one year earlier. Conversely, the number of neXtProt PE2,3,4 proteins, termed the "missing proteins" (MPs), has been reduced from 2949 to 2129 since 2016 through efforts throughout the community, including the chromosome-centric HPP. PeptideAtlas is the source of uniformly reanalyzed raw mass spectrometry data for neXtProt; PeptideAtlas added 495 canonical proteins between 2018 and 2019, especially from studies designed to detect hard-to-identify proteins. Meanwhile, the Human Protein Atlas has released version 18.1 with immunohistochemical evidence of expression of 17 000 proteins and survival plots as part of the Pathology Atlas. Many investigators apply multiplexed SRM-targeted proteomics for quantitation of organ-specific popular proteins in studies of various human diseases. The 19 teams of the Biology and Disease-driven B/D-HPP published a total of 160 publications in 2018, bringing proteomics to a broad array of biomedical research.

9.
Pediatr Emerg Care ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268961

RESUMO

OBJECTIVES: Falls are the leading cause of pediatric injury and account for the majority of emergency department injury visits, costing US $5 billion in medical costs annually. Epidemiology of pediatric falls has primarily been studied at single hospital centers and has not been analyzed statewide. We assessed pediatric falls across Maryland and geographically mapped them by census tract and block group. METHODS: The study used Maryland Health Services Cost Review Commission discharge data to retrospectively analyze the demographics and cross-sectional incidence rates of fall injuries in Maryland from 2013 to 2015. Geographical clusters were calculated for pediatric falls in Maryland and Baltimore City. RESULTS: From 2013 to 2015, Maryland hospitals discharged 738,819 pediatric patients, of whom 77,113 had fall injuries. Falls were more prevalent among males (56%), white race (55%), and patients with public insurance (56%). Over this period, 2 children who presented with fall injuries died. The incidence of falls did not vary from 2013 (27,481 children) to 2014 (27,261) and 2015 (26,451). Mapping fall injuries across Maryland identified Baltimore City as the primary cluster and rural pockets as secondary clusters of high incidence rates. Baltimore City maps showed a stable high-incidence cluster in the southwest region across all 3 years. CONCLUSIONS: Pediatric fall injuries comprise a large volume of emergency department visits yet have a low mortality. Geographic mapping shows that fall incidence varies across the state and persists over time. Statewide geographic information can be used to focus resource management and target prevention strategies.

10.
Science ; 364(6447): 1264-1267, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31249054

RESUMO

Adding energy to a system through transient stirring usually leads to more disorder. In contrast, point-like vortices in a bounded two-dimensional fluid are predicted to reorder above a certain energy, forming persistent vortex clusters. In this study, we experimentally realize these vortex clusters in a planar superfluid: a 87Rb Bose-Einstein condensate confined to an elliptical geometry. We demonstrate that the clusters persist for long time periods, maintaining the superfluid system in a high-energy state far from global equilibrium. Our experiments explore a regime of vortex matter at negative absolute temperatures and have relevance for the dynamics of topological defects, two-dimensional turbulence, and systems such as helium films, nonlinear optical materials, fermion superfluids, and quark-gluon plasmas.

11.
Clin Chim Acta ; 495: 611-624, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31176645

RESUMO

Oncoproteomics is the systematic study of cancer samples using omics technologies to detect changes implicated in tumorigenesis. Recent progress in oncoproteomics is already opening new avenues for the identification of novel biomarkers for early clinical stage cancer detection, targeted molecular therapies, disease monitoring, and drug development. Such information will lead to new understandings of cancer biology and impact dramatically on the future care of cancer patients. In this review, we will summarize the advantages and limitations of the key technologies used in (onco)proteogenomics, (the Omics Pipeline), explain how they can assist us in understanding the biology behind the overarching "Hallmarks of Cancer", discuss how they can advance the development of precision/personalised medicine and the future directions in the field.

12.
J Proteome Res ; 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31046287

RESUMO

Human olfactory receptors (ORs) are seven-pass transmembrane G-protein coupled receptors (GPCR) involved in smell perception and many other signaling pathways. They are primarily expressed in the olfactory epithelium and ectopically expressed in several other organs and tissues. neXtProt contains 4 PE1 (protein existence 1, evidenced at the protein level) ORs, determined on the basis of either protein interaction data (i.e., OR1D4 and OR2AG1) or convincing genetic, haplotype, or biochemical data (i.e., OR1D2 and OR2J3). Not a single OR currently qualifies for neXtProt PE1 status based on mass spectrometry (MS) evidence. Many reasons for this absence of MS-based identification have been proposed, including (i) confined or spatiotemporal or developmental expression, (ii) low copy number, (iii) OR repertoire gene silencing, and (iv) limited tissue availability. OR transmembrane domains (TMDs) inherently limit MS identification because the hydrophobic nature restricts the access of trypsin to potential cleavage sites. Equally, the extremely low frequency or lack of accessible arginine and lysine residues in TMDs renders trypsin cleavage ineffective. Here, we demonstrate an analytical approach specifically focused on the hydrophilic (trypsin-accessible) domains of ORs [i.e., with all transmembrane segments and anchored peptides excluded). We predicted the ability of OR soluble (hydrophilic) domains to yield 2 or more >9 amino acids (aa) length unique mapping (unique to a protein only), non-nested (peptides with varying length at the N or C terminal but containing the same core sequence), leucine/isoleucine (I/L) switch examined (I and L have same mass and cannot be distinguished by MS) tryptic peptides. Our analysis showed that ∼58% of the human OR proteome could potentially generate tryptic peptides that satisfy current the Human Proteome Project data interpretation guidelines (version 2.1) when no missed cleavages are allowed and increases to ∼78% when one missed cleavage is allowed. The utilization of current biological data (adjuvant genomics, expression profile, transcriptomics, epigenome silencing data, etc.) and the adoption of a non-conventional proteomics approach (e.g., Confetti multiprotease digestion, CNBr cleavage of TMDs, and more-extreme chromatographic and MS methods) could aid in the detection of the remaining ORs.

13.
Reproduction ; 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31117052

RESUMO

Stallions experience lower per cycle conception rates compared to other livestock species, largely because they are selected for breeding based on athletic prowess and not reproductive fitness. Mares are seasonal breeders, and pregnancies cannot be detected until 10-14 days post-cover via transrectal ultrasonography. This means the detection of stallion fertility fluctuations is delayed by at least two weeks, which within the short breeding season employed by the Thoroughbred horse breeding industry, can prove quite costly. For these reasons, there is increased demand for robust laboratory assays aimed at the accurate assessment of stallion fertility. This paper reviews our existing knowledge concerning the molecular mechanisms that underpin the functional competence of stallion spermatozoa, highlighting the relative importance of oxidative stress, DNA damage, sperm proteomics and RNA profile. We also consider the way in which fundamental improvements in our understanding of stallion sperm biology are informing the identification and development of possible biomarkers of fertility and thus avenues for the development of specific assays for fertility prediction.

14.
Gut ; 68(6): 1115-1126, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30944110

RESUMO

Patients with Crohn's disease commonly develop ileal and less commonly colonic strictures, containing various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment, predominantly fibrotic strictures currently require endoscopic balloon dilation or surgery. Therefore, differentiation of the main components of a stricturing lesion is key for defining the therapeutic management. The role of endoscopy to diagnose the nature of strictures is limited by the superficial inspection of the intestinal mucosa, the lack of depth of mucosal biopsies and by the risk of sampling error due to a heterogeneous distribution of inflammation and fibrosis within a stricturing lesion. These limitations may be in part overcome by cross-sectional imaging techniques such as ultrasound, CT and MRI, allowing for a full thickness evaluation of the bowel wall and associated abnormalities. This systematic literature review provides a comprehensive summary of currently used radiologic definitions of strictures. It discusses, by assessing only manuscripts with histopathology as a gold standard, the accuracy for diagnosis of the respective modalities as well as their capability to characterise strictures in terms of inflammation and fibrosis. Definitions for strictures on cross-sectional imaging are heterogeneous; however, accuracy for stricture diagnosis is very high. Although conventional cross-sectional imaging techniques have been reported to distinguish inflammation from fibrosis and grade their severity, they are not sufficiently accurate for use in routine clinical practice. Finally, we present recent consensus recommendations and highlight experimental techniques that may overcome the limitations of current technologies.


Assuntos
Doença de Crohn/epidemiologia , Obstrução Intestinal/epidemiologia , Intestino Delgado/patologia , Imagem Multimodal/métodos , Comorbidade , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/epidemiologia , Constrição Patológica/patologia , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Estudos Transversais , Técnicas de Imagem por Elasticidade/métodos , Feminino , Fibrose/diagnóstico por imagem , Fibrose/epidemiologia , Humanos , Incidência , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/patologia , Intestino Delgado/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Masculino , Prognóstico , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia Doppler/métodos
15.
Rural Remote Health ; 19(1): 4743, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30825873

RESUMO

INTRODUCTION: This study aimed to demonstrate that teleneurology consultations conducted via tablet technology are an efficient and cost-effective means of managing acute neurologic emergencies at community-based hospitals and that utilizing such technology yields high community physician satisfaction. METHOD: During a 39-month period, Vanderbilt University Medical Center in Tennessee USA, provided teleneurology services to 10 community-based hospitals that lacked adequate neurology coverage. Hospitalists at one community-based hospital were not comfortable treating any patient with a neurologic symptom, resulting in 100% of those patients being transferred. This facility now retains more than 60% of neurology patients. For less than US$1200, these hospitals were able to meet the only capital expenditure required to launch this service: the purchase of handheld tablet computers. Real-time teleneurology consultations were conducted via tablet using two-way video conferencing, radiologic image sharing, and medical record documentation. Community physicians were regularly surveyed to assess satisfaction. RESULTS: From February 2014 to May 2017, 3626 teleneurology consultations were conducted. Community physicians, in partnership with neurologists, successfully managed 87% of patients at the community-based hospital. Only 13% of patients required transfer to another facility for a higher level of care. The most common diagnoses included stroke (34%), seizure (11%), and headache/migraine (6%). The average time for the neurologist to answer a request for consultation page and connect with the community physician was 10.6 minutes. Ninety-one percent of community physicians were satisfied or somewhat satisfied with the overall service. CONCLUSION: In the assessment of neurology patients, tablets are a more cost-effective alternative to traditional telehealth technologies. The devices promote efficiency in consultations through ease of use and low transfer rates, and survey results indicate community physician satisfaction.


Assuntos
Pessoal de Saúde/estatística & dados numéricos , Satisfação no Emprego , Neurologia/organização & administração , Consulta Remota/estatística & dados numéricos , Telemedicina/organização & administração , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia , Padrões de Prática Médica
16.
Neurorehabil Neural Repair ; 33(5): 375-383, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30913964

RESUMO

BACKGROUND: Recent evidence from both monkey and human studies suggests that the reticulospinal tract may contribute to recovery of arm and hand function after stroke. In this study, we evaluated a marker of reticulospinal output in stroke survivors with varying degrees of motor recovery. METHODS: We recruited 95 consecutive stroke patients presenting 6 months to 12 years after their index stroke, and 19 heathy control subjects. Subjects were asked to respond to a light flash with a rapid wrist flexion; at random, the flash was paired with either a quiet or loud (startling) sound. The mean difference in electromyogram response time after flash with quiet sound compared with flash with loud sound measured the StartReact effect. Upper limb function was assessed by the Action Research Arm Test (ARAT), spasticity was graded using the Modified Ashworth Scale (MAS) and active wrist angular movement using an electrogoniometer. RESULTS: StartReact was significantly larger in stroke patients than healthy participants (78.4 vs 45.0 ms, P < .005). StartReact showed a significant negative correlation with the ARAT score and degree of active wrist movement. The StartReact effect was significantly larger in patients with higher spasticity scores. CONCLUSION: We speculate that in some patients with severe damage to their corticospinal tract, recovery led to strengthening of reticulospinal connections and an enhanced StartReact effect, but this did not occur for patients with milder impairment who could use surviving corticospinal connections to mediate recovery.

19.
AJR Am J Roentgenol ; 212(3): 490-496, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30620681

RESUMO

OBJECTIVE: The purposes of this article are to describe the creation of template report formats and content for a variety of abdominal and pelvic CT and MRI examinations and discuss a review-of-systems approach to text and avoidance of pitfalls of report templates. CONCLUSION: Organ system-specific report templates for CT and MRI incorporate radiologist preferences. Disease-specific report templates are created from these reports to provide a consistent radiologist and referring physician experience across the report templates.

20.
J Neurol ; 266(3): 667-679, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30631918

RESUMO

Mills' syndrome is an idiopathic, slowly progressive, spastic hemiparesis. We describe three cases that have been under review for a minimum of 11 years (range 11-19). In all patients, symptoms started in a leg, with a mean age of onset of 59 years (range 53-63). The only abnormality on laboratory investigations was a mildly elevated CSF protein in one case. MRI demonstrated focal T2 hyper-intensity located eccentrically in the cervical cord ipsilateral to the symptomatic side. No cerebral abnormality was demonstrated. Whilst visual and somatosensory evoked potentials were unremarkable, motor evoked potentials were abnormal in all patients: central motor conduction times were significantly prolonged unilaterally in two patients and bilaterally but asymmetrically in the third. Beta-band (15-30 Hz) intermuscular coherence, a potentially more sensitive method of assessing upper motor neuron integrity, was absent unilaterally in one patient and bilaterally in the other two. One patient developed amyotrophy and thus a picture of amyotrophic lateral sclerosis after 16 years, suggesting that Mills' syndrome is part of the motor neuron disease spectrum. Both amyotrophy and subclinical contralateral upper motor neuron disease can therefore be features of Mills' syndrome. However, even with the most sensitive electrodiagnostic techniques, unilateral upper motor neuron disease can remain the only abnormality for as long as 10 years. We conclude that whilst Mills' syndrome should be classified as a motor neuron disorder, it is a distinct nosological entity which can be distinguished from amyotrophic lateral sclerosis, upper motor neuron-dominant amyotrophic lateral sclerosis and primary lateral sclerosis. We propose diagnostic criteria for Mills' syndrome, and estimate a point prevalence of at least 1.2:1,000,000 based on our well-defined referral population in the North of England.


Assuntos
Potencial Evocado Motor/fisiologia , Hemiplegia/fisiopatologia , Doença dos Neurônios Motores/fisiopatologia , Idoso , Eletromiografia , Feminino , Hemiplegia/etiologia , Hemiplegia/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA