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1.
Surgeon ; 22(3): 150-153, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38331688

RESUMO

INTRODUCTION: Kidney transplantation is the treatment of choice for patients with end stage renal disease. The primary aim of this study was to assess the demographics of deceased kidney donors over the last ten years and to assess for gender variations in deceased donor demographics over an extended period. METHODS: A retrospective data analysis was carried out using data from the national renal transplant database. All deceased donors who donated a kidney between 1st January 2012 and 31st December 2021 were included. Data points extracted included gender, age, cause of death and month of death. Descriptive analyses were carried out using Excel v16.67. RESULTS: A total of 1219 kidneys from 650 donors were donated over the ten-year period. The mean donor age was 44.01 years (range 1-74 years). The most common cause of death overall was subarachnoid haemorrhage (SAH), which was the cause of death in 27.8 % of donors (n = 180). Male donors accounted for 57.8 % of donors overall (n = 376). Variation in causes of death was observed between male and female donors, and between younger and older donors. 9 % of male deaths were from suicide compared with 5 % of female deaths. 6 % of male deaths were due to a traumatic head injury, with this accounting for 2 % of female deaths. Deaths due to assault made up 2 % of male donor deaths, but were not a cause of death for any female donors. CONCLUSION: SAH and intracranial bleeds were the most common cause of death in both groups for deceased donor renal transplantation. Incidence of suicide as cause of death in deceased donors is rising in males.


Assuntos
Transplante de Rim , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Adolescente , Estudos Retrospectivos , Idoso , Adulto Jovem , Irlanda/epidemiologia , Criança , Pré-Escolar , Lactente , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Causas de Morte
2.
Health Promot Pract ; : 15248399231182161, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37366650

RESUMO

To address the reality that LGBTQ+ (lesbian, gay, bisexual, transgender, queer, intersex, asexual, and others) students remain more likely to experience harm, harassment, and violence at school as well as miss school due to feeling unsafe and the fact that students identifying as transgender, nonbinary, and gender-nonconforming (TNBGNC) are at even greater risk of bullying, harassment, and significant mental health concerns, Chicago Public Schools' (CPS) Office of Student Health and Wellness (OSHW) created a novel professional development (PD) requirement in 2019, entitled "Supporting Transgender, Nonbinary, and Gender Nonconforming Students." The PD, a recorded webinar encouraging independent time for reflection and planning, takes an intersectional approach and is required of all CPS staff members across the entire district. A pre- and postevaluation of the PD, guided by the Kirkpatrick model, was completed by 19,503 staff members. The findings from this evaluation show that staff members significantly increased their knowledge, showed statistically significant gain in self-reported skills, and articulated key actions they could take toward sustaining an environment that fosters skill implementation and culture change more broadly. Findings reveal that a culture that supports staff members in learning from their mistakes can help to encourage staff members to employ gender-inclusive behaviors such as asking individuals for their pronouns and using gender-neutral pronouns. This districtwide mandatory PD approach shows value in influencing staff members' thinking and behaviors known to be supportive of TNBGNC students and may serve as a model for other school districts looking to build capacity to support TNBGNC students.

3.
Clin Radiol ; 77(12): e826-e834, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36270867

RESUMO

The new Royal College of Radiologists (RCR) undergraduate curriculum and the impending introduction of a universal General Medical Council (GMC) medical licensing assessment (MLA) for all undergraduates in the UK heralds a new era of undergraduate radiology education. This is a practical guide to both implementing and delivering undergraduate radiology education using our experience and the available literature. It aims to provide ideas so that more universities and radiologists can integrate radiology into everyday learning and are ready to embrace the new RCR curriculum and GMC MLA. Allied to this, strategies are provided to show how to encourage early undergraduate interest in a career in radiology.


Assuntos
Educação de Graduação em Medicina , Radiologia , Humanos , Radiologia/educação , Currículo , Radiografia , Radiologistas
4.
Clin Radiol ; 76(4): 247-261, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33423761

RESUMO

The last decade has seen a paradigm shift in medical oncology treatment with the rise of novel systemic agents, principally molecular targeted therapy and immunotherapy. These new groups of anti-cancer treatment have revolutionised the prognostic landscape for certain patient cohorts with advanced disease, and it is hoped that through ongoing extensive clinical research, significant survival benefits may be demonstrated in the majority of tumour types. However, radiological response assessment of these new agents has become more nuanced for radiologists, as the behaviour of both responding and progressing tumour burden can be more diverse than with conventional chemotherapy. Additionally, radiologists need to be aware of adverse events associated with these treatments as some side effects carry a high morbidity/mortality and may manifest radiologically before they become clinically apparent. This review discusses radiological response assessment and adverse events associated with these novel agents, which have become fundamental aspects of systemic oncological therapy.


Assuntos
Imunoterapia/efeitos adversos , Terapia de Alvo Molecular/efeitos adversos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Progressão da Doença , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Metástase Neoplásica/diagnóstico por imagem , Neoplasias/patologia , Tomografia Computadorizada por Raios X , Carga Tumoral
5.
Neuroimage ; 204: 116220, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31546046

RESUMO

Understanding the neural underpinning of conscious perception remains one of the primary challenges of cognitive neuroscience. Theories based mostly on studies of the visual system differ according to whether the neural activity giving rise to conscious perception occurs in modality-specific sensory cortex or in associative areas, such as the frontal and parietal cortices. Here, we search for modality-specific conscious processing in the auditory cortex using a bistable stream segregation paradigm that presents a constant stimulus without the confounding influence of physical changes to sound properties. ABA_ triplets (i.e., alternating low, A, and high, B, tones, and _ gap) with a 700 ms silent response period after every third triplet were presented repeatedly, and human participants reported nearly equivalent proportions of 1- and 2-stream percepts. The pattern of behavioral responses was consistent with previous studies of visual and auditory bistable perception. The intermittent response paradigm has the benefit of evoking spontaneous perceptual switches that can be attributed to a well-defined stimulus event, enabling precise identification of the timing of perception-related neural events with event-related potentials (ERPs). Significantly more negative ERPs were observed for 2-streams compared to 1-stream, and for switches compared to non-switches during the sustained potential (500-1000 ms post-stimulus onset). Further analyses revealed that the negativity associated with switching was independent of switch direction, suggesting that spontaneous changes in perception have a unique neural signature separate from the observation that 2-stream percepts evoke more negative ERPs than 1-stream. Source analysis of the sustained potential showed activity associated with these differences originating in anterior superior temporal gyrus, indicating involvement of the ventral auditory pathway that is important for processing auditory objects.


Assuntos
Vias Auditivas/fisiologia , Percepção Auditiva/fisiologia , Potenciais Evocados/fisiologia , Desempenho Psicomotor/fisiologia , Lobo Temporal/fisiologia , Adulto , Mapeamento Encefálico , Eletroencefalografia , Feminino , Humanos , Masculino , Adulto Jovem
6.
Phys Rev Lett ; 125(10): 102502, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32955302

RESUMO

The low-spin structure of the semimagic ^{64}Ni nucleus has been considerably expanded: combining four experiments, several 0^{+} and 2^{+} excited states were identified below 4.5 MeV, and their properties established. The Monte Carlo shell model accounts for the results and unveils an unexpectedly complex landscape of coexisting shapes: a prolate 0^{+} excitation is located at a surprisingly high energy (3463 keV), with a collective 2^{+} state 286 keV above it, the first such observation in Ni isotopes. The evolution in excitation energy of the prolate minimum across the neutron N=40 subshell gap highlights the impact of the monopole interaction and its variation in strength with N.

7.
Clin Radiol ; 75(12): 903-913, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32782128

RESUMO

Prostate-specific membrane antigen (PSMA)-based positron-emission tomography (PET)-computed tomography (CT) has shown great promise in prostate cancer imaging. This technique has demonstrated particular utility in the staging of high-risk primary cancer and in the localisation of recurrent disease. The use of fluorine-18 PSMA-1007 is advantageous, as it is excreted via the hepatobiliary system rather than urinary and the longer half-life of fluorine-18 compared to gallium tracers, allows for PSMA imaging in centres without a gallium generator. However, imaging with this tracer is not without flaws and areas of ambiguity remain. In this article, the biodistribution, clinical indications, and pearls of 18F-PSMA-1007 PET-CT in patients with prostate cancer will be discussed, as well as the potential pitfalls in the reporting of these studies.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Radioisótopos de Flúor , Humanos , Masculino , Estadiamento de Neoplasias , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos
8.
Forensic Sci Med Pathol ; 16(3): 515-518, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32394207

RESUMO

Secondary aortoduodenal fistula (AEF), although less rare than its primary form, is an uncommon and frequently lethal cause of gastrointestinal (GI) bleeding. We report a case of fatal GI hemorrhage in a woman with a remote history of endovascular graft repair of an abdominal aortic aneurysm. Postmortem examination included computed tomography (PMCT) and CT angiography (PMCTA), which revealed air in the aorta, loss of the fat plane between the aorta and duodenum, and direct extravasation of contrast from the aorta into the duodenum. To our knowledge, this is the first published report of secondary AEF diagnosed by PMCT and confirmed with PMCTA. We propose a set of imaging criteria by which PMCTA can be used to supplant traditional anatomical dissection in the medicolegal investigation of deaths due to AEF.


Assuntos
Aorta/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Duodeno/diagnóstico por imagem , Fístula Intestinal/diagnóstico por imagem , Fístula Vascular/diagnóstico por imagem , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/cirurgia , Evolução Fatal , Feminino , Humanos
9.
Phys Rev Lett ; 123(10): 102501, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31573317

RESUMO

An extensive, model-independent analysis of the nature of triaxial deformation in ^{76}Ge, a candidate for neutrinoless double-beta (0νßß) decay, was carried out following multistep Coulomb excitation. Shape parameters deduced on the basis of a rotational-invariant sum-rule analysis provided considerable insight into the underlying collectivity of the ground-state and γ bands. Both sequences were determined to be characterized by the same ß and γ deformation parameter values. In addition, compelling evidence for low-spin, rigid triaxial deformation in ^{76}Ge was obtained for the first time from the analysis of the statistical fluctuations of the quadrupole asymmetry deduced from the measured E2 matrix elements. These newly determined shape parameters are important input and constraints for calculations aimed at providing, with suitable accuracy, the nuclear matrix elements relevant to 0νßß.

10.
Clin Radiol ; 74(6): 480-486, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30871716

RESUMO

AIM: To assess foundation doctors' experiences of undergraduate radiology teaching within the UK and preferences for radiology teaching delivery. MATERIALS AND METHODS: This was a retrospective multicentre study of foundation doctors. A questionnaire, designed using the Royal College of Radiologists Undergraduate Radiology Curriculum, was completed to determine how prepared foundation doctors felt in image interpretation by their undergraduate teaching. For this, agreement with statements was graded using a five-point Likert scale. Open and closed questions were used to assess preferences for teaching delivery. RESULTS: The study involved 150 foundation doctors from 29 medical schools. The majority "strongly agreed" or "agreed" that undergraduate training gave them confidence in interpreting most basic chest and abdominal radiographs. Confidence was less for skeletal radiographs and trauma computed tomography (CT). Seventy-seven percent wished they had had more radiology teaching. The three most important topics to be included in teaching were chest radiograph, CT, and abdominal radiograph interpretation. Small group teaching and integration into clinical teaching received the highest number of votes for preferred teaching delivery method. Ninety-two percent felt radiologists were best suited to deliver teaching. CONCLUSION: In general, foundation doctors felt undergraduate teaching prepared them well for chest and abdominal radiograph interpretation, but less so for skeletal radiography and CT. The majority felt more undergraduate radiology teaching would be beneficial, and that this should be delivered by radiologists in either small group sessions or integrated into clinical teaching.


Assuntos
Atitude do Pessoal de Saúde , Educação de Graduação em Medicina/métodos , Médicos/estatística & dados numéricos , Radiologia/educação , Currículo , Humanos , Médicos/psicologia , Estudos Retrospectivos , Inquéritos e Questionários , Reino Unido
11.
BMC Nephrol ; 20(1): 279, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345158

RESUMO

BACKGROUND: Scleroderma Renal Crisis (SRC) is associated with significant morbidity and mortality. While prednisone is strongly associated with SRC, there are no previous large cohort studies that have evaluated ace inhibitor (ACEi) calcium channel blocker (CCB), angiotensin receptor blocker (ARB), endothelin receptor blocker (ERB), non-steroidal anti-inflammatory drug (NSAID), fluticasone, or mycophenolate mofetil (MMF) use in systemic sclerosis (SSc) and the risk of SRC. METHODS: In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the use of ACEi, ARB, CCB, NSAID, ERB, fluticasone, and MMF after SSc diagnosis for 31 cases who subsequently developed SRC to 322 SSc without SRC disease controls. RESULTS: ACEi was associated with an increased risk for SRC adjusted for age, race, and prednisone use [odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6-10.2, P = 0.003]. On stratified analyses, ACEi was only associated with SRC in the presence [OR 5.3, 95% CI 1.1-29.2, p = 0.03], and not the absence of proteinuria. In addition, a doubling of ACEi dose [61% vs. 12%, p < 0.001) and achieving maximum ACEi dose [45% vs. 4%, p < 0.001] after SSc diagnosis was associated with future SRC. CCB, ARB, NSAIDs, ERB, fluticasone, and MMF use were not significantly associated with SRC. CONCLUSION: ACEi use at SSC diagnosis was associated with an increased risk for SRC. Results suggest that it may be a passive marker of known SRC risk factors, such as proteinuria, or evolving disease. SSC patients that require ACEi should be more closely monitored for SRC.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Hipertensão Renal/induzido quimicamente , Hipertensão Renal/epidemiologia , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco
12.
Surgeon ; 17(1): 1-5, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29807673

RESUMO

INTRODUCTION: Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients. METHODS: Twenty-three paediatric to adult EBKTs were performed by the Irish National Kidney Transplant Service between 1990 and 2016. The primary outcome variable was long-term en-bloc allograft survival rate. Secondary outcome variables were incidence of allograft thrombosis, incidence of delayed graft function, overall patient survival and serum creatinine at most recent follow-up. Outcomes were compared to single kidney transplant recipients from the same time period. RESULTS: Mean donor age was 1.8 ± 0.97 years (range: 7 months to 3 years). Recipient age was 46 ± 12 years. Mean follow-up was 133 ± 64 months (range: 36-264). Overall graft survival was 100%, 91% and 80% after 1, 5 and 10 years respectively, compared to 92%, 79% and 61% in single kidney transplant recipients (p = 0.04). There were 5 cases of allograft failure, 3 due to death from unrelated causes. Median time to graft failure was 108 months (range: 36-172). Mean serum creatinine was 72.6 ± 21.6 µmol/l after the follow-up period. There were no cases of graft thrombosis or delayed graft function. Overall survival was 96.4%, 88.0%, 76.23% and 50.5% at 1, 5, 10 and 20 years respectively. CONCLUSION: En-bloc paediatric kidney transplantation is associated with excellent long-term allograft and patient survival and is a feasible strategy for increasing the transplant donor pool in carefully selected recipients.


Assuntos
Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Doadores de Tecidos , Adulto , Fatores Etários , Idoso , Pré-Escolar , Feminino , Humanos , Lactente , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos/classificação , Resultado do Tratamento
13.
Calcif Tissue Int ; 103(5): 529-539, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29943187

RESUMO

Significant fracture history in children is defined as having at least one vertebral fracture, at least 2 fractures by age 10, or at least 3 fractures by age 19. Between September 2011 and December 2014, clinical data were collected on children with a significant fracture history that attended a major Australian children's hospital. Fifty-six patients were identified as having 305 fractures in total, including 44 vertebral fractures. 18% of patients (10/56) were diagnosed with osteogenesis imperfecta (OI) by a bone health expert, molecular testing or both, and they sustained 23% of all fractures (71/305). Analysis of serum bone biochemistry showed all median values to be within a normal range and no clinically significant differences between patients with and without OI. The DXA and pQCT derived bone mineral density (BMD) and bone mineral content (BMC) Z scores were reduced overall. DXA derived total body and lumbar spine areal BMD-for-age and BMC-for-age Z scores were significantly lower in children who had vertebral fractures or who were later diagnosed with OI. Similarly, pQCT performed on radii and tibiae showed Z scores significantly less than zero. pQCT-derived limb muscle cross sectional area Z scores were significantly lower in the OI subgroup. In conclusion, this study describes the bone phenotype of children referred to a tertiary hospital clinic for recurrent fractures and highlights a subset of children with previously undiagnosed OI, but a larger cohort without classic OI. Thus it can be clinically challenging to differentiate between children with OI type 1 (mild phenotype) and non-OI children without bone densitometry and genetic testing. We conclude that recurrent fractures in children should prompt a comprehensive bone and systemic health assessment to eliminate an underlying pathology.


Assuntos
Fraturas Ósseas/diagnóstico , Fraturas Ósseas/etiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Osteogênese Imperfeita/complicações , Recidiva
14.
Phys Chem Chem Phys ; 19(30): 19794-19806, 2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28643835

RESUMO

We compute molecular continuum orbitals in the single center expansion scheme. We then employ these orbitals to obtain molecular Auger rates and single-photon ionization cross sections to study the interaction of N2 with Free-Electron-Laser (FEL) pulses. The nuclei are kept fixed. We formulate rate equations for the energetically allowed molecular and atomic transitions and we account for dissociation through additional terms in the rate equations. Solving these equations for different parameters of the FEL pulse, allows us to identify the most efficient parameters of the FEL pulse for obtaining the highest contribution of double core hole states (DCH) in the final atomic ion fragments. Finally we identify the contribution of DCH states in the electron spectra and show that the DCH state contribution is more easily identified in the photo-ionization rather than the Auger transitions.

15.
Am J Forensic Med Pathol ; 38(4): 362-366, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29068812

RESUMO

Iatrogenic vascular injury is a potentially serious complication of surgical procedures. Here we report a case of delayed fatal intra-abdominal hemorrhage because of electrocautery injury of a right external iliac artery. The decedent, a 31-year-old woman, died suddenly on postoperative day 1 after a laparoscopic staging operation for an ovarian tumor. Her past medical history included a recent diagnosis of a microinvasive carcinoma in the background of a mucinous cystic neoplasm of the right ovary. Postmortem examination revealed a young woman with evidence of emergency intervention, recent laparoscopic pelvic surgery, and pale hypostasis limited to the back surfaces of the body. The internal examination confirmed the postmortem computed tomography findings of a large amount of blood in the pelvic and abdominal cavities and evidence of recent surgical intervention. The soft tissues around the aorta and major pelvic vessels showed electrocautery change and marked perivascular hemorrhage preferentially surrounding the right external iliac artery. Histological examination of the vascular bundle showed an electrocautery injury of the arterial wall: transmural necrosis, acute inflammation, and hemorrhage. In this report, we offer an approach to a postmortem examination in postoperative deaths with emphasis on deaths due to iatrogenic vascular injuries and discuss the rationale for determining the manner of death.


Assuntos
Eletrocoagulação/efeitos adversos , Artéria Ilíaca/lesões , Erros Médicos , Hemorragia Pós-Operatória/etiologia , Adulto , Evolução Fatal , Feminino , Hemoperitônio/etiologia , Humanos , Neoplasias Ovarianas/cirurgia
16.
Environ Monit Assess ; 188(1): 34, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26676410

RESUMO

Sediment contaminants were monitored in Milford Haven Waterway (MHW) since 1978 (hydrocarbons) and 1982 (metals), with the aim of providing surveillance of environmental quality in one of the UK's busiest oil and gas ports. This aim is particularly important during and after large-scale investment in liquefied natural gas (LNG) facilities. However, the methods inevitably have changed over the years, compounding the difficulties of coordinating sampling and analytical programmes. After a review by the MHW Environmental Surveillance Group (MHWESG), sediment hydrocarbon chemistry was investigated in detail in 2010. Natural Resources Wales (NRW) contributed their MHW data for 2007 and 2012, collected to assess the condition of the Special Area of Conservation (SAC) designated under the European Union Habitats Directive. Datasets during 2007-2012 have thus been more comparable. The results showed conclusively that a MHW-wide peak in concentrations of sediment polycyclic aromatic hydrocarbons (PAHs), metals and other contaminants occurred in late 2007. This was corroborated by independent annual monitoring at one centrally located station with peaks in early 2008 and 2011. The spatial and temporal patterns of recovery from the 2007 peak, shown by MHW-wide surveys in 2010 and 2012, indicate several probable causes of contaminant trends, as follows: atmospheric deposition, catchment runoff, sediment resuspension from dredging, and construction of two LNG terminals and a power station. Adverse biological effects predictable in 2007 using international sediment quality guidelines were independently tested by data from monitoring schemes of more than a decade duration in MHW (starfish, limpets) and in the wider SAC (grey seals). Although not proving cause and effect, many of these potential biological receptors showed a simultaneous negative response to the elevated 2007 contamination following intense dredging activity in 2006. Wetland bird counts were typically at a peak in the winter of 2005-2006 previous to peak dredging. In the following winter 2006-2007, shelduck in the Pembroke River showed their lowest winter count, and spring 2007 was the largest ever drop in numbers of shelduck broods across MHW between successive breeding seasons. Wigeon counts in the Pembroke River were low in 2006-2007 and in late 2012 after further dredging nearby. These results are strongly supported by PAH data reported previously from invertebrate bioaccumulation studies in MHW 2007-2010, themselves closely reflecting sediment trends for PAHs in the Pembroke River and Angle Bay.


Assuntos
Monitoramento Ambiental , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Animais , Invertebrados , Metais/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Rios , Estações do Ano , País de Gales
17.
J Musculoskelet Neuronal Interact ; 15(2): 161-70, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26032208

RESUMO

Neurofibromatosis Type 1 (NF1) is a genetic neurocutaneous disorder with multisystem manifestations, including a predisposition to tumor formation and bone dysplasias. Studies over the last decade have shown that NF1 can also be associated with significant motor deficits, such as poor coordination, low muscle tone, and easy fatigability. These have traditionally been ascribed to developmental central nervous system and cognitive deficits. However, recent preclinical studies have also illustrated a primary role for the NF1 gene product in muscle growth and metabolism; these findings are consistent with clinical studies demonstrating reduced muscle size and muscle weakness in individuals with NF1. Currently there is no evidence-based intervention for NF1 muscle and motor deficiencies; this review identifies key research areas where improved mechanistic understanding could unlock new therapeutic options.


Assuntos
Transtornos dos Movimentos/fisiopatologia , Músculo Esquelético/patologia , Neurofibromatose 1/patologia , Adolescente , Adulto , Criança , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Músculo Esquelético/fisiopatologia , Neurofibromatose 1/fisiopatologia , Neurofibromatose 1/terapia , Adulto Jovem
18.
Forensic Sci Med Pathol ; 11(4): 596-600, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26464132

RESUMO

Aortoenteric fistula (AEF) is an uncommon source of upper gastrointestinal (GI) tract hemorrhage, commonly occurring in persons with previous aortic surgery. Non-surgery related AEFs (primary AEFs) may occur in association with atherosclerotic lesions, infections, malignancies, or, rarely, result from penetrating/eroding foreign bodies. Given its rarity, primary AEF is not commonly considered in the pathologist's preliminary list of differential diagnoses at the commencement of an autopsy; however, the use of postmortem cross-sectional imaging may allow for the identification of primary AEF as a reasonable differential diagnoses prior to conventional autopsy. The current case outlines the forensic presentation, postmortem computed tomography (PMCT) features, and autopsy findings of a recent case of primary AEF resulting in lethal gastrointestinal hemorrhage. In such cases, PMCT features supporting primary AEF as the underlying cause of death include an atherosclerotic aneurysm abutting a segment of the GI tract with no definite soft tissue plane of separation, luminal GI contents of similar radiographic density to the aortic contents, lack of previous aortic surgery, and lack of a competing explanation for GI hemorrhage or a competing cause of death. Deaths from massive enteric hemorrhage without a medical history to suggest an underlying cause for the hemorrhage would fall under medicolegal jurisdiction and may, by examination of scene and circumstances alone, initially seem suspicious. This case demonstrates how PMCT could be used by a team of expert forensic radiologists and forensic pathologists to rapidly feedback vital information on the cause and manner of death to the criminal justice system.


Assuntos
Doenças da Aorta/diagnóstico por imagem , Morte Súbita/etiologia , Duodenopatias/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Fístula Intestinal/diagnóstico por imagem , Idoso , Doenças da Aorta/patologia , Duodenopatias/patologia , Humanos , Fístula Intestinal/patologia , Masculino , Tomografia Computadorizada por Raios X
19.
Forensic Sci Med Pathol ; 11(4): 558-63, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26242774

RESUMO

Angioedema is an episodic swelling of the deep dermis, subcutis, and/or submucosal tissue due to an increase in local vascular permeability. Swelling may involve skin, respiratory, and gastrointestinal tracts. The most commonly involved areas are the periorbital region and the lips. Here we report a case of a fatal laryngeal obstruction due to angioedema likely caused by an angiotensin-converting-enzyme inhibitor. The decedent, a 58-year-old man, was witnessed developing sudden facial swelling and acute respiratory difficulties quickly followed by unresponsiveness. His past medical history suggested that this was his second episode of angioedema without urticaria. Postmortem examination revealed a complete laryngeal obstruction in the absence of infection, neoplasm, or autoimmune disease. Postmortem computed tomography of the head and neck showed a complete obstruction of the upper airway. Based on the current understanding of the pathophysiology of different types of angioedema, we will suggest a workup of angioedema without urticaria in the forensic setting and offer readers resources they can use in their practice.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Angioedema/induzido quimicamente , Angioedema/patologia , Doenças da Laringe/induzido quimicamente , Obstrução das Vias Respiratórias/patologia , Angioedema/diagnóstico por imagem , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Evolução Fatal , Humanos , Doenças da Laringe/diagnóstico por imagem , Doenças da Laringe/patologia , Masculino , Pessoa de Meia-Idade , Radiografia
20.
Eur Cell Mater ; 27: 98-109; discussion 109-111, 2014 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-24488823

RESUMO

Current clinical delivery of recombinant human bone morphogenetic proteins (rhBMPs) utilises freeze-dried collagen. Despite effective new bone generation, rhBMP via collagen can be limited by significant complications due to inflammation and uncontrolled bone formation. This study aimed to produce an alternative rhBMP local delivery system to permit more controllable and superior rhBMP-induced bone formation. Cylindrical porous poly(lactic-co-glycolic acid) (PLGA) scaffolds were manufactured by thermally-induced phase separation. Scaffolds were encapsulated with anabolic rhBMP-2 (20 µg) ± anti-resorptive agents: zoledronic acid (5 µg ZA), ZA pre-adsorbed onto hydroxyapatite microparticles, (5 µg ZA/2% HA) or IkappaB kinase (IKK) inhibitor (10 µg PS-1145). Scaffolds were inserted in a 6-mm critical-sized femoral defect in Wistar rats, and compared against rhBMP-2 via collagen. The regenerate region was examined at 6 weeks by 3D microCT and descriptive histology. MicroCT and histology revealed rhBMP-induced bone was more restricted in the PLGA scaffolds than collagen scaffolds (-92.3% TV, p < 0.01). The regenerate formed by PLGA + rhBMP-2/ZA/HA showed comparable bone volume to rhBMP-2 via collagen, and bone mineral density was +9.1% higher (p < 0.01). Local adjunct ZA/HA or PS-1145 significantly enhanced PLGA + rhBMP-induced bone formation by +78.2% and +52.0%, respectively (p ≤ 0.01). Mechanistically, MG-63 human osteoblast-like cells showed cellular invasion and proliferation within PLGA scaffolds. In conclusion, PLGA scaffolds enabled superior spatial control of rhBMP-induced bone formation over clinically-used collagen. The PLGA scaffold has the potential to avoid uncontrollable bone formation-related safety issues and to customise bone shape by scaffold design. Moreover, local treatment with anti-resorptive agents incorporated within the scaffold further augmented rhBMP-induced bone formation.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Proteína Morfogenética Óssea 2/metabolismo , Regeneração Óssea , Difosfonatos/farmacologia , Regeneração Tecidual Guiada , Imidazóis/farmacologia , Alicerces Teciduais/química , Animais , Proteína Morfogenética Óssea 2/genética , Linhagem Celular , Fêmur/efeitos dos fármacos , Fêmur/cirurgia , Humanos , Quinase I-kappa B/antagonistas & inibidores , Ácido Láctico/farmacologia , Masculino , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Wistar , Ácido Zoledrônico
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