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OBJECTIVES: To evaluate the outcomes of subadventitial stenting (SS) around occluded stents for recanalizing in-stent chronic total occlusions (IS-CTOs). BACKGROUND: There is little evidence on the outcomes of SS for IS-CTO. METHODS: We examined the outcomes of SS for IS-CTO PCI at 14 centers between July 2011 and June 2017, and compared them to historical controls recanalized using within-stent stenting (WSS). Target-vessel failure (TVF) on follow-up was the endpoint of this study, and was defined as a composite of cardiac death, target-vessel myocardial infarction, and target-vessel revascularization. RESULTS: During study period, 422 IS-CTO PCIs were performed, of which 32 (7.6%) were recanalized with SS, usually when conventional approaches failed. The most frequent CTO vessel was the right coronary artery (72%). Mean J-CTO score was 3.1 ± 0.9. SS was antegrade in 53%, and retrograde in 47%. Part of the occluded stent was crushed in 37%, while the whole stent was crushed in 63%. Intravascular imaging was used in 59%. One patient (3.1%) suffered tamponade. Angiographic follow-up was performed in 10/32 patients: stents were patent in six cases, one had mild neointimal hyperplasia, and three had severe restenosis at the SS site. Clinical follow-up was available for 29/32 patients for a mean of 388 ± 303 days. The 24-month incidence of TVF was 13.8%, which was similar to historical controls treated with WSS (19.5%, P = 0.49). CONCLUSIONS: SS is rarely performed, usually as last resort, to recanalize complex IS-CTOs. It is associated with favorable acute and mid-term outcomes, but given the small sample size of our study additional research is warranted.
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Oclusão Coronária/terapia , Reestenose Coronária/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea , Idoso , Austrália , Canadá , Doença Crônica , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/etiologia , Oclusão Coronária/mortalidade , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/mortalidade , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/mortalidade , Desenho de Prótese , Sistema de Registros , Retratamento , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Ultrassonografia de Intervenção , Estados Unidos , Grau de Desobstrução VascularRESUMO
Cavernous hemangioma in the sellar region is quite rare with only a handful of cases being reported in the English literature. Its clinical manifestations and imaging characteristics can mimic those of a pituitary adenoma. We report two cases of recurrent sellar lesions, both of which were clinically suspected of being pituitary adenomas but histologically confirmed as cavernous hemangiomas. The first case is of a 67-year-old female whose initial resection was diagnosed as "venous angioma". Neuroimaging performed 27 years later demonstrated significant growth of the lesion involving the right cavernous sinus and encasing the right internal carotid artery. The patient then underwent transsphenoidal endoscopic resection of the mass. At the time of the surgery, the lesion was noted to be quite vascular. The second case is a 48-year-old female who underwent emergency resection of a pituitary mass following an apoplectic event. On follow-up 4 years later, the patient reported recurrence of galactorrhea, and MRI had demonstrated regrowth of the mass. She subsequently underwent subtotal resection of the mass. At the time of surgery, brisk bleeding was noted in the operative area. The above two cases demonstrate that cavernous hemangiomas in the sellar region can clinically and radiologically mimic pituitary adenoma and should be considered in the differential diagnosis of hemorrhagic sellar mass.â©.
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Adenoma/diagnóstico , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Adenoma/patologia , Idoso , Diagnóstico Diferencial , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Humanos , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologiaRESUMO
AIMS: Elderly patients with sinus node dysfunction (SND) are at increased risk of falls with possible injuries. However, the incidence of these adverse events and its reduction after permanent pacemaker (PPM) implantation are not known. METHODS AND RESULTS: Eighty-seven patients (mean [SD] age 75.4 [8.3] years, 51% women) with SND and an indication for cardiac pacing were included and were examined by a standardized interview targeting fall history. The incidence and total number of falls, falls with injury, falls requiring treatment, and falls resulting in a fracture were assessed for the time period of 12 months before (retrospectively) and after PPM implantation (prospectively). Furthermore, symptoms such as syncope, dizziness, and dyspnea were evaluated before and after PPM implantation. The implantation of a PPM was associated with a reduced proportion of patients experiencing at least one fall by 71% (from 53 to 15%, P < 0.001) and a reduction of the absolute number of falls by 90% (from 127 to 13, P < 0.001) during the 12 months before vs. after PPM implant. Falls with injury (28 vs. 10%, P = 0.005), falls requiring medical attention (31 vs. 8%, P < 0.001), and falls leading to fracture (8 vs. 0%, P = 0.013) were similarly reduced. Notably, fewer patients had syncope (4 vs. 45%, P < 0.001) and dizziness after PPM implantation (12 vs. 45%, P < 0.001). CONCLUSION: Falls, fall-related injuries, and fall-related fractures are frequent in SND patients. Permanent pacemaker implantation is associated with a significantly reduced risk of these adverse events, although no causal relationship could be established due to the study design.
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Acidentes por Quedas/prevenção & controle , Estimulação Cardíaca Artificial , Marca-Passo Artificial , Síndrome do Nó Sinusal/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Síndrome do Nó Sinusal/complicações , Síndrome do Nó Sinusal/diagnóstico , Síndrome do Nó Sinusal/fisiopatologia , Suíça , Fatores de Tempo , Resultado do TratamentoRESUMO
The histopathological features of leucoencephalopathy caused by illicit drugs (such as opioids and cocaine) are well documented in acute cases but not in long-survival cases. There are several hypotheses about the pathogenesis of this disorder, including hypoperfusion, direct drug toxicity resulting from the neurotoxic effects of the drug itself or contaminants in the illicit drug vehicle. We reviewed the post mortem findings in five males (aged 24 to 56 years, with survival intervals ranging from 7 days to 5 months) with a history of illicit drug use and concomitant fatal white matter changes. The histological characteristics of leucoencephalopathy vary with survival period. Prominent axonal injury and axonal spheroids were observed with shorter survival and spongiform changes becoming apparent with longer survival (acute and chronic incomplete infarct pattern). Necrosis was present in all cases and its appearance changed with longer survival (acute and chronic complete infarct pattern). Significant primary demyelination was not observed. These observations suggest that the primary defect in this leucoencephalopathy is hypoxic-ischemic injury, predominantly in the white matter. Spongiform leucoencephalopathy likely represents the longer-survival incomplete infarct pattern and is observed with polydrug abuse.
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Encéfalo/patologia , Hipóxia-Isquemia Encefálica/patologia , Drogas Ilícitas/efeitos adversos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/patologia , Adulto , Autopsia , Humanos , Hipóxia-Isquemia Encefálica/etiologia , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/patologia , Adulto JovemRESUMO
HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches.
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Anemia Refratária com Excesso de Blastos/diagnóstico , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Neoplasias Cutâneas/diagnóstico , Anemia Refratária com Excesso de Blastos/patologia , Anemia Refratária com Excesso de Blastos/virologia , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Anticorpos Anti-HTLV-I/imunologia , Anticorpos Anti-HTLV-II/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Humanos , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/virologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologiaRESUMO
BACKGROUND: Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. METHODS: We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. FINDINGS: Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0·004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0·033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0·001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2·02 (95% CI 1·04-3·85; p=0·038) and 3·98 (1·71-9·26; p=0·001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. INTERPRETATION: An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours. FUNDING: C17 Research Network, Genome Canada, b.r.a.i.n.child, Mitchell Duckman, Tal Doron and Suri Boon foundations.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Genômica , Receptores Notch/biossíntese , Tumor Rabdoide/genética , Teratoma/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Lactente , Masculino , Prognóstico , Receptores Notch/genética , Tumor Rabdoide/patologia , Fatores de Risco , Transdução de Sinais/genética , Teratoma/patologiaRESUMO
BACKGROUND: Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of lysosomal metabolism. The clinical phenotypic spectrum encompasses overlapping features of variable severity and is suggestive of individual single sulfatase deficiencies (i.e., metachromatic leukodystrophy, mucopolysaccharidosis, and X-linked ichthyosis). CASE REPORT: We describe a 3-year-old male with severe hypotonia, developmental regression and progressive neurodegeneration, coarse facial features, nystagmus (from ocular albinism), and dysmyelinating motor sensory neuropathy. Ethics approval was obtained from the Western University Ontario. RESULTS: Extensive investigative work-up identified deficiencies of multiple sulfatases: heparan sulfate sulfamidase: 6.5 nmoles/mg/protein/17 hour (reference 25.0-75.0), iduronate-2-sulfate sulfatase: 9 nmol/mg/protein/4 hour (reference 31-110), and arylsulfatase A: 3.8 nmoles/hr/mg protein (reference 22-50). The identification of compound heterozygous pathogenic mutations in the SUMF1 gene c.836 C>T (p.A279V) and c.1045C>T (p.R349W) confirmed the diagnosis of MSD. CONCLUSION: The complex clinical manifestations of MSD and the unrelated coexistence of ocular albinism as in our case can delay diagnosis. Genetic counselling should be provided to all affected families.
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Albinismo Ocular/complicações , Albinismo Ocular/diagnóstico , Doença da Deficiência de Múltiplas Sulfatases/complicações , Doença da Deficiência de Múltiplas Sulfatases/diagnóstico , Albinismo Ocular/genética , Pré-Escolar , Diagnóstico Diferencial , Humanos , Masculino , Doença da Deficiência de Múltiplas Sulfatases/genéticaRESUMO
Background: Modern medicine requires intensive research to find new diagnostic and therapeutic solutions. Recently, upconverting nanoparticles (UCNPs) doped with lanthanide ions have attracted significant attention. Methods: The efficient internalization of UCNPs by cells was confirmed, and their precise cellular localization was determined by electron microscopy and confocal studies. Results: UCNPs colocalized only with specific organelles, such as early endosomes, late endosomes and lysosomes. Furthermore, experiments with chemical inhibitors confirmed the involvement of endocytosis in UCNPs internalization and helped select several mechanisms involved in internalization. Exposure to selected UCNPs concentrations did not show significant cytotoxicity, induction of oxidative stress or ultrastructural changes in cells. Conclusion: This study suggests that UCNPs offer new diagnostic options for biomedical infrared imaging.
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Elementos da Série dos Lantanídeos , Nanopartículas , Distribuição Tecidual , Elementos da Série dos Lantanídeos/química , Diagnóstico por Imagem , Nanopartículas/químicaRESUMO
BACKGROUND AND PURPOSE: Controversy surrounds the need for routine hospital admission for transient ischemic attack. The Monash Transient Ischemic Attack Triaging Treatment (M3T) model adopts rapid management in the emergency department followed by outpatient management prioritized by stroke mechanism. We compared safety and processes of care between M3T and the previous model of routine admission. METHODS: Study cohorts consisted of patients managed with M3T (2004-2007) and the previous model (2003-2004). We determined 90-day stroke outcome using clinical and medical record review and data linkage to the population level state-wide hospital discharge morbidity database. We compared models of care using risk difference analysis, followed by logistic regression to adjust for previous indicators of risk. Secondary outcomes were proportions admitted, proportions undergoing carotid ultrasound, times to ultrasound and revascularization, and medication prescription. RESULTS: In M3T (mean age, 64.7±14.7) 85/488 (17.4%) patients were admitted compared with 117/169 (62.9%) in the previous model (mean age, 72.5±13.9). With near-complete follow-up, 90-day stroke outcome was 1.50% (95% confidence interval, 0.73%-3.05%) in M3T and 4.67% (95% confidence interval, 2.28%-9.32%) in the previous model (P=0.03). Compared with the previous model, the adjusted odds ratio of stroke for M3T was 0.46 (95% confidence interval, 0.12-1.68; P=0.24). M3T was associated with greater proportions undergoing carotid ultrasound (P<0.001) and receiving antiplatelet therapy (P=0.005). CONCLUSIONS: The M3T system was associated with low 90-day stroke outcome in transient ischemic attack patients, providing proof of concept that these patients may be managed safely without routine hospital admission using a closely supervised protocol in the emergency department.
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Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/terapia , Pacientes Ambulatoriais , Triagem/métodos , Idoso , Artérias Carótidas/diagnóstico por imagem , Estudos de Coortes , Testes Diagnósticos de Rotina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , UltrassonografiaRESUMO
Six infants in an Old Order Amish pedigree were observed to be affected with endocrine-cerebro-osteodysplasia (ECO). ECO is a previously unidentified neonatal lethal recessive disorder with multiple anomalies involving the endocrine, cerebral, and skeletal systems. Autozygosity mapping and sequencing identified a previously unknown missense mutation, R272Q, in ICK, encoding intestinal cell kinase (ICK). Our results established that R272 is conserved across species and among ethnicities, and three-dimensional analysis of the protein structure suggests protein instability due to the R272Q mutation. We also demonstrate that the R272Q mutant fails to localize at the nucleus and has diminished kinase activity. These findings suggest that ICK plays a key role in the development of multiple organ systems.
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Doenças Ósseas/genética , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Endócrino/genética , Etnicidade/genética , Mutação , Proteínas Serina-Treonina Quinases/genética , Animais , Autopsia , Doenças Ósseas/sangue , Doenças Ósseas/patologia , Encéfalo/enzimologia , Doenças do Sistema Nervoso Central/patologia , Sequência Conservada , Doenças do Sistema Endócrino/sangue , Doenças do Sistema Endócrino/patologia , Éxons , Feminino , Genes Recessivos , Humanos , Rim/enzimologia , Fígado/enzimologia , Masculino , Linhagem , Proteínas Serina-Treonina Quinases/sangue , Irmãos , Especificidade da Espécie , SíndromeRESUMO
The present article reports a case involving a 58-year-old man without cardiovascular risk factors who was admitted to hospital with acute coronary syndrome. Coronary angiography revealed high-grade arteriosclerotic stenosis of the mid-left anterior descending coronary artery and 80% proximal intermediate branch stenosis, which were treated using three drug-eluting stents. Churg-Strauss syndrome was diagnosed based on the patient's history of asthma, sinusitis, eosinophilia, nasal polyps, transient radiological pulmonary infiltrations and transient paresthesia over the left tibia, and eosinophilic pericardial effusion and eosinophilic infiltrations revealed in a myocardial biopsy. Treatment with prednisone was initiated, followed by treatment with cyclophosphamide. Eosinophil levels returned to normal after nine days of treatment. There is evidence that Churg-Strauss syndrome may promote arteriosclerosis.
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OBJECTIVE: To determine the predictive value of the ABCD(2) score for early risk of stroke in Australian patients who have had transient ischaemic attack (TIA). DESIGN, PARTICIPANTS AND SETTING: Cohort study of 512 consecutive patients with suspected TIA referred by the emergency department to the acute stroke unit (in accordance with the TIA pathway) of an urban tertiary hospital in Melbourne, Victoria, between 1 June 2004 and 30 November 2007. MAIN OUTCOME MEASURES: Overall accuracy, estimated by the area under the curve (AUC) of receiver operating characteristic plots (of true positive rate v false positive rate), and sensitivity, specificity, predictive values and likelihood ratios at prespecified cut-off ABCD(2) scores for stroke within 2, 7 and 90 days. RESULTS: 24 patients were excluded because their symptoms lasted more than 24 hours. All included patients were reviewed by a stroke physician; TIA was confirmed in 301/488 (61.7%). Most (289/301; 96.0%) had complete follow-up. Stroke occurred in 4/292 patients (1.37%; 95% CI, 0.37%-3.47%) within 2 days and 7/289 (2.42%; 95% CI, 0.98%-4.93%) within 90 days; no patient had a stroke between 2 and 7 days. The AUCs for stroke in patients with confirmed TIA were 0.80 (95% CI, 0.68-0.91) and 0.62 (95% CI, 0.40-0.83) for stroke within 2 days and 90 days, respectively. At a cut-off of ≥ 5, the ABCD(2) score had modest specificity for stroke within 2 days (0.58) and 90 days (0.58), but positive predictive values (2 days, 0.03; 90 days, 0.04) and positive likelihood ratios (2 days, 2.40; 90 days, 1.71) were both poor. The score performed similarly poorly at other prespecified cut-off scores. CONCLUSIONS: Given its poor predictive value, the use of the ABCD(2) score alone may not be dependable for guiding clinical treatment decisions or service organisation in an Australian tertiary setting. Validation in other Australian settings is recommended before it can be applied with confidence.
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Indicadores Básicos de Saúde , Ataque Isquêmico Transitório/complicações , Acidente Vascular Cerebral/etiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Estudos de Coortes , Complicações do Diabetes/complicações , Feminino , Humanos , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Fatores de Tempo , VitóriaRESUMO
BACKGROUND: Grade 3 ischemia during ST elevation myocardial infarction (STEMI) is defined as ST elevation with distortion of the terminal portion of the QRS on electrocardiogram (ECG). The aim of this study was to evaluate the effect of ischemic grade on cardiac magnetic resonance (CMR) imaging infarct characteristics such as infarct size, microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and myocardial salvage. METHODS: Patients with STEMI treated with primary percutaneous coronary intervention had a 12-lead ECG on presentation for analysis of ischemic grade. Gadolinium-enhanced CMR imaging was performed within 7 days to assess infarct size, MVO, IMH, and myocardial salvage. RESULTS: Of the 37 patients enrolled in the study, grade 3 ischemia was present in 32%. Those with grade 3 ischemia had higher peak troponin I levels (P = .013), more MVO (P < .001), more IMH (P < .001), larger infarct size (P = .025), and less myocardial salvage (P = .012). Regression analysis found that grade 3 ischemia, infarct size, and peak troponin I level were significantly associated with MVO and IMH. CONCLUSION: Grade 3 ischemia on the admission ECG during STEMI is closely associated with the development of severe microvascular damage on CMR imaging.
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Eletrocardiografia/métodos , Imagem Cinética por Ressonância Magnética/métodos , Microvasos/patologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/patologia , Idoso , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
BACKGROUND: persistent ST elevation after reperfused ST elevation myocardial infarction (STEMI) is believed to be related to poor microvascular perfusion. Cardiac magnetic resonance imaging (CMR) can evaluate microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) both of which represent severe microvascular damage, have independent prognostic value and are dynamic and evolving over the first 48hours after reperfusion. The aim of this study was to assess whether the development of MVO or IMH has an impact upon ST segment resolution. METHODS: patients undergoing primary percutaneous coronary intervention (PCI) for STEMI had serial 12 lead electrocardiograms (ECG) from one hour after PCI until discharge. Persistent single lead maximal residual ST elevation (maxSTE) at each time point was calculated. ST segment deterioration (re-elevation) was calculated on each ECG until discharge compared with one hour post PCI ECG. CMR was performed within seven days post infarct utilising T2 weighted imaging to evaluate culprit artery area at risk (AAR) and IMH. Gadolinium delayed enhancement CMR quantified infarct size and MVO. RESULTS: in the 41 patients studied 58% had MVO and 41% had IMH. ST segment deterioration was more common in those with MVO or IMH (p=0.03 and p=0.008 respectively). MaxSTE was higher at each time point after PCI in those with MVO but only became statistically significant after 24hours. The measurement of maxSTE at 48 or 72hours after revascularisation provided the best correlation with the combination of infarct size, AAR, MVO and intramyocardial haemorrhage. CONCLUSION: microvascular injury as defined on CMR is associated with dynamic changes and persistence of ST segment elevation in the first 72hours after reperfusion.
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Circulação Coronária , Eletrocardiografia , Imageamento por Ressonância Magnética , Microcirculação , Infarto do Miocárdio , Reperfusão Miocárdica , Idoso , Angioplastia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Radiografia , Fatores de TempoRESUMO
BACKGROUND: Coronary artery emboli can occur from a number of rare causes such as arterial thrombo-embolus or septic embolus. This diagnosis generally requires multi-modal imaging including echocardiography, computed tomography, or invasive coronary angiography. Septic coronary emboli is an extremely rare consequence of infective endocarditis (IE), having been reported in <1% of all cases. CASE SUMMARY: A 54-year-old previously healthy Tibetan monk presented feeling generally unwell and lethargic. Electrocardiogram demonstrated sinus rhythm, third-degree atrioventricular block with a left bundle branch escape. Initial transthoracic and transoesophageal echocardiography demonstrated vegetations on the aortic and tricuspid valve as well as intra-myocardial abscess. Coronary angiography revealed septic embolus involving the septal perforator coronary artery. He underwent surgical replacement of the infected valves and debridement and repair of a ventricular septal defect. DISCUSSION: Infective endocarditis can predispose to a range of cardiac pathology. This case demonstrates that patients can present with cardiac conduction disease from a septic embolus involving a coronary artery as a complication of IE.
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The study aim was to investigate the pharmacokinetics of single high doses and repeated therapeutic doses of fluticasone furoate (FF) and batefenterol (BAT; a bifunctional muscarinic antagonist and ß2 -agonist) administered in combination (BAT/FF) or as monotherapy. In this open-label, 6-period, crossover study of 48 subjects, the treatment sequences were (1) single high-dose BAT/FF 900/300 µg followed by repeated therapeutic doses of BAT/FF 300/100 µg (once daily for 7 days); (2) single high-dose BAT 900 µg administered concurrently with FF 300 µg; (3) single high-dose BAT 900 µg followed by repeated therapeutic-dose BAT 300 µg; (4) single high-dose FF 300 µg followed by repeated therapeutic-dose FF 100 µg; (5) single high-dose FF 300 µg (magnesium stearate); and (6) single high-dose FF/vilanterol 300/75 µg. Plasma FF area under the plasma drug concentration-time curve (AUC) was reduced after single high-dose BAT/FF versus FF alone (ratio of geometric least squares means: 0.79; 90% confidence interval: 0.75-0.83). After repeat dosing, FF AUC at the lower therapeutic dosage was similar for BAT/FF and FF (primary endpoint; AUC geometric least squares means: 1.03). Adverse events were minor, the most common being cough. These data support the feasibility of developing BAT/inhaled corticosteroid triple therapy in a single inhaler.
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Androstadienos/administração & dosagem , Carbamatos/administração & dosagem , Quinolonas/administração & dosagem , Adulto , Androstadienos/efeitos adversos , Androstadienos/farmacocinética , Área Sob a Curva , Carbamatos/efeitos adversos , Carbamatos/farmacocinética , Estudos Cross-Over , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Quinolonas/efeitos adversos , Quinolonas/farmacocinética , Adulto JovemRESUMO
We used single nucleotide polymorphism (SNP) microarrays to investigate the cause of a symptomatic epilepsy syndrome in a group of seven distantly related Old Order Mennonite children. Autozygosity mapping was inconclusive, but closer inspection of the data followed by formal SNP copy number analyses showed that all affected patients had homozygous deletions of a single SNP (rs721575) and their parents were hemizygous for this marker. The deleted SNP marked a larger deletion encompassing exons 9-13 of LYK5, which encodes STE20-related adaptor protein, a pseudokinase necessary for proper localization and function of serine/threonine kinase 11 (a.k.a. LKB1). Homozygous LYK5 deletions were associated with polyhydramnios, preterm labour and distinctive craniofacial features. Affected children had large heads, infantile-onset intractable multifocal seizures and severe psychomotor retardation. We designated this condition PMSE syndrome (polyhydramnios, megalencephaly and symptomatic epilepsy). Thirty-eight percent (N = 16) of affected children died during childhood (ages 7 months to 6 years) from medical complications of the disorder, which included status epilepticus, congestive heart failure due to atrial septal defect and hypernatremic dehydration due to diabetes insipidus. A single post-mortem neuropathological study revealed megalencephaly, ventriculomegaly, cytomegaly and extensive vacuolization and astrocytosis of white matter. There was abundant anti-phospho-ribosomal S6 labelling of large cells within the frontal cortex, basal ganglia, hippocampus and spinal cord, consistent with constitutive activation of the mammalian target of rapamycin (mTOR) signalling pathway in brain.
Assuntos
Encéfalo/anormalidades , Epilepsia/genética , Deleção de Genes , Proteínas do Tecido Nervoso/genética , Poli-Hidrâmnios/genética , Proteínas Serina-Treonina Quinases/genética , Adolescente , Adulto , Sequência de Bases , Encéfalo/patologia , Criança , Pré-Escolar , Mapeamento Cromossômico/métodos , Epilepsia/patologia , Evolução Fatal , Feminino , Genótipo , Humanos , Lactente , Imageamento por Ressonância Magnética , Dados de Sequência Molecular , Fenótipo , Poli-Hidrâmnios/patologia , Polimorfismo de Nucleotídeo Único , Gravidez , Transtornos Psicomotores/genética , Transtornos Psicomotores/patologia , SíndromeRESUMO
The mechanical properties of barnacle base plates were measured using a punch test apparatus, with the purpose of examining the effect that the base plate flexural rigidity may have on adhesion mechanics. Base plate compliance was measured for 43 Balanus amphitrite (=Amphibalanus amphitrite) barnacles. Compliance measurements were used to determine flexural rigidity (assuming a fixed-edge circular plate approximation) and composite modulus of the base plates. The barnacles were categorized by age and cement type (hard or gummy) for statistical analyses. Barnacles that were 'hard' (> or =70% of the base plate thin, rigid cement) and 'gummy' (>30% of the base plate covered in compliant, tacky cement) showed statistically different composite moduli but did not show a difference in base plate flexural rigidity. The average flexural rigidity for all barnacles was 0.0020 Nm (SEM +/- 0.0003). Flexural rigidity and composite modulus did not differ significantly between 3-month and 14-month-old barnacles. The relatively low flexural rigidity measured for barnacles suggests that a rigid punch approximation is not sufficient to account for the contributions to adhesion mechanics due to flexing of real barnacles during release.