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Hemoglobin (Hb) disorders are among the most common monogenic diseases affecting nearly 7% of the world population. Among various Hb disorders, approximately 1.5% of the world population carries ß-thalassemia (ß-Thal), affecting 40,000 newborns every year. Early screening and a timely diagnosis are essential for ß-thalassemia patients for the prevention and management of later clinical complications. However, in Africa, Southern Europe, the Middle East, and Southeast Asia, where ß-thalassemia is most prevalent, the diagnosis and screening for ß-thalassemia are still challenging due to the cost and logistical burden of laboratory diagnostic tests. Here, we present Gazelle, which is a paper-based microchip electrophoresis platform that enables the first point-of-care diagnostic test for ß-thalassemia. We evaluated the accuracy of Gazelle for the ß-Thal screening across 372 subjects in the age range of 4-63 years at Apple Diagnostics lab in Mumbai, India. Additionally, 30 blood samples were prepared to mimic ß-Thal intermediate and ß-Thal major samples. Gazelle-detected levels of Hb A, Hb F, and Hb A2 demonstrated high levels of correlation with the results reported through laboratory gold standard high-performance liquid chromatography (HPLC), yielding a Pearson correlation coefficient = 0.99. This ability to obtain rapid and accurate results suggests that Gazelle may be suitable for the large-scale screening and diagnosis of ß-Thal.
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Antílopes , Hemoglobinopatías , Talasemia beta , Recién Nacido , Humanos , Animales , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Talasemia beta/diagnóstico , Talasemia beta/epidemiología , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/epidemiología , Cromatografía Líquida de Alta PresiónRESUMEN
BACKGROUND: Resting brain connectivity is a crucial component of human behavior demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, a recently identified critical reproductive hormone, can alter activity in certain brain structures but its effects on resting brain connectivity and networks in humans remain elusive. METHODS: We determined the effects of kisspeptin on resting brain connectivity (using functional neuroimaging) and behavior (using psychometric analyses) in healthy men, in a randomized double-blinded 2-way placebo-controlled study. RESULTS: Kisspeptin's modulation of the default mode network (DMN) correlated with increased limbic activity in response to sexual stimuli (globus pallidus r = 0.500, P = 0.005; cingulate r = 0.475, P = 0.009). Furthermore, kisspeptin's DMN modulation was greater in men with less reward drive (r = -0.489, P = 0.008) and predicted reduced sexual aversion (r = -0.499, P = 0.006), providing key functional significance. Kisspeptin also enhanced key mood connections including between the amygdala-cingulate, hippocampus-cingulate, and hippocampus-globus pallidus (all P < 0.05). Consistent with this, kisspeptin's enhancement of hippocampus-globus pallidus connectivity predicted increased responses to negative stimuli in limbic structures (including the thalamus and cingulate [all P < 0.01]). CONCLUSION: Taken together, our data demonstrate a previously unknown role for kisspeptin in the modulation of functional brain connectivity and networks, integrating these with reproductive hormones and behaviors. Our findings that kisspeptin modulates resting brain connectivity to enhance sexual and emotional processing and decrease sexual aversion, provide foundation for kisspeptin-based therapies for associated disorders of body and mind. FUNDING: NIHR, MRC, and Wellcome Trust.
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Emociones/efectos de los fármacos , Kisspeptinas/administración & dosificación , Conducta Sexual/efectos de los fármacos , Administración Intravenosa , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Conectoma , Estudios Cruzados , Método Doble Ciego , Emociones/fisiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Trastornos Mentales/tratamiento farmacológico , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Placebos/administración & dosificación , Psicometría , Descanso/fisiología , Conducta Sexual/fisiología , Disfunciones Sexuales Fisiológicas/tratamiento farmacológico , Adulto JovenRESUMEN
PURPOSE: To review the clinical and biochemical characteristics and clinical outcome of patients presenting with pituitary apoplexy to a tertiary centre. METHODS: We retrospectively reviewed the clinical features, predisposing factors, biochemistry and clinical outcome of patients presenting with pituitary apoplexy to Imperial College Healthcare NHS Trust between 1991 to 2015. RESULTS: We identified 64 patients with pituitary apoplexy (more complete clinical records were available in 52 patients). The median age at presentation was 46.7 years (IQR 31.5-57.0 years). Pituitary apoplexy was the first presentation of pituitary disease in 38/52 of patients and predisposing factors were identified in 28/52. Pituitary apoplexy predominantly occurred in patients with non-functioning pituitary adenomas (47/52). Headache was most commonly described as sudden-onset, severe, lateralising to the frontal or temporal regions. Symptoms of meningeal irritation were reported in 7/18 and visual abnormalities in 22/35. A pre-treatment serum cortisol <100nmol/l was recorded in 12/31 of patients. All patients with visual disturbance had some resolution of their visual symptoms whether managed surgically (14/14) or conservatively (5/5), although pituitary endocrine function did not fully recover in any patient. CONCLUSIONS: In conclusion, these data describe the clinical features of pituitary apoplexy to aid the clinician in diagnosing this rare emergency presentation of pituitary disease. Prospective multicentre studies of the presentation of pituitary apoplexy are required to further characterise presentation and outcomes.
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Background: An inability to recall recent conversations often indicates impaired episodic memory retrieval. It may also reflect a failure of attentive registration of spoken sentences which leads to unsuccessful memory encoding. The hypothesis was that patients complaining of impaired memory would demonstrate impaired function of "multiple demand" (MD) brain regions, whose activation profile generalizes across cognitive domains, during speech registration in naturalistic listening conditions. Methods: Using functional MRI, brain activity was measured in 22 normal participants and 31 patients complaining of memory impairment, 21 of whom had possible or probable Alzheimer's disease (AD). Participants heard a target speaker, either speaking alone or in the presence of distracting background speech, followed by a question to determine if the target speech had been registered. Results: Patients performed poorly at registering verbal information, which correlated with their scores on a screening test of cognitive impairment. Speech registration was associated with widely distributed activity in both auditory cortex and in MD cortex. Additional regions were most active when the target speech had to be separated from background speech. Activity in midline and lateral frontal MD cortex was reduced in the patients. A central cholinesterase inhibitor to increase brain acetylcholine levels in half the patients was not observed to alter brain activity or improve task performance at a second fMRI scan performed 6-11 weeks later. However, individual performances spontaneously fluctuated between the two scanning sessions, and these performance differences correlated with activity within a right hemisphere fronto-temporal system previously associated with sustained auditory attention. Conclusions: Midline and lateralized frontal regions that are engaged in task-dependent attention to, and registration of, verbal information are potential targets for transcranial brain stimulation to improve speech registration in neurodegenerative conditions.
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Purpose To validate a random forest method for segmenting cerebral white matter lesions (WMLs) on computed tomographic (CT) images in a multicenter cohort of patients with acute ischemic stroke, by comparison with fluid-attenuated recovery (FLAIR) magnetic resonance (MR) images and expert consensus. Materials and Methods A retrospective sample of 1082 acute ischemic stroke cases was obtained that was composed of unselected patients who were treated with thrombolysis or who were undergoing contemporaneous MR imaging and CT, and a subset of International Stroke Thrombolysis-3 trial participants. Automated delineations of WML on images were validated relative to experts' manual tracings on CT images, and co-registered FLAIR MR imaging, and ratings were performed by using two conventional ordinal scales. Analyses included correlations between CT and MR imaging volumes, and agreements between automated and expert ratings. Results Automated WML volumes correlated strongly with expert-delineated WML volumes at MR imaging and CT (r2 = 0.85 and 0.71 respectively; P < .001). Spatial-similarity of automated maps, relative to WML MR imaging, was not significantly different to that of expert WML tracings on CT images. Individual expert WML volumes at CT correlated well with each other (r2 = 0.85), but varied widely (range, 91% of mean estimate; median estimate, 11 mL; range of estimated ranges, 0.2-68 mL). Agreements (κ) between automated ratings and consensus ratings were 0.60 (Wahlund system) and 0.64 (van Swieten system) compared with agreements between individual pairs of experts of 0.51 and 0.67, respectively, for the two rating systems (P < .01 for Wahlund system comparison of agreements). Accuracy was unaffected by established infarction, acute ischemic changes, or atrophy (P > .05). Automated preprocessing failure rate was 4%; rating errors occurred in a further 4%. Total automated processing time averaged 109 seconds (range, 79-140 seconds). Conclusion An automated method for quantifying CT cerebral white matter lesions achieves a similar accuracy to experts in unselected and multicenter cohorts.
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Encéfalo/diagnóstico por imagen , Encéfalo/patología , Leucoaraiosis/diagnóstico por imagen , Leucoaraiosis/patología , Accidente Cerebrovascular/patología , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucoaraiosis/etiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Accidente Cerebrovascular/complicaciones , Sustancia BlancaRESUMEN
BACKGROUND: There is growing evidence that maximal surgical resection of primary intrinsic brain tumours is beneficial, both by improving progression free and overall survival and also by facilitating postoperative chemotherapy and radiotherapy. Hence, there has been an increase in the popularity of real-time intraoperative imaging in brain tumour surgery. The complex theatre arrangements, prohibitive cost and prolonged theatre time of intraoperative MRI have restricted its application. By comparison, intraoperative three-dimensional ultrasound (i3DUS) is user friendly, cost-effective and portable and adds little to surgical time. However, operator-dependent image quality and image interpretation remain limiting factors to the wider application of this technique. The aim of this study was to explore objective i3DUS image analysis and its potential therapeutic role in brain tumour surgery. METHODS: A prospective, observational study was undertaken (approved by the local Research and Ethics Committee prior to recruitment). Biopsies were taken from the solid, necrotic, periphery and brain/tumour interface of intrinsic primary brain tumours. Digital i3DUS images were analysed to extract quantitative parameters from these regions of interest (ROI) in the i3DUS images. These were then correlated with the histology of the relevant specimens. The histopathologist was blinded to the imaging findings. RESULTS: Ninety-seven patients (62 males; mean 54 years) with varying gliomas (84 high grade) were included. Two hundred and ninety regions of interest were analysed. Mean pixel brightness (MPB) and standard deviation (SD) were correlated with histological features. Close correlations were noted between MPB and cellularity, and SD and intrinsic cellular diversity. CONCLUSIONS: MPB and SD are objective measures reflecting the sensitivity of i3DUS in detecting the presence and extent of intrinsic brain tumours. They indirectly suggest heterogeneity, cellularity and invasiveness, providing information of the nature of the tumour, and also reflect the sensitivity of intraoperative US to detect the presence of residual intrinsic brain tumours. Development of this paradigm will enhance i3DUS use as an adjunct in brain tumour surgery. Optimizing its intraoperative application will impact surgical resection and, hence, patient outcome.
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BACKGROUND: Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS: Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS: We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS: Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING: National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).
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Emociones/efectos de los fármacos , Kisspeptinas/administración & dosificación , Sistema Límbico/diagnóstico por imagen , Sistema Límbico/fisiología , Conducta Sexual/efectos de los fármacos , Adulto , Método Doble Ciego , Humanos , MasculinoRESUMEN
CONTEXT: The natural history and the optimum management of patients with nonfunctioning pituitary adenomas (NFPAs) are unclear. OBJECTIVE: Our objective was to characterize the natural history of patients with NFPAs managed conservatively. DESIGN AND PATIENTS: We conducted a retrospective analysis of patients presenting to a tertiary referral centre between 1986 and 2009. Patients with pituitary adenomas and no clinical or biochemical evidence of hormonal hypersecretion were included. Those presenting with apoplexy or a radiological follow-up period of less than 1 year were excluded. The pituitary imaging for all patients was re-examined by two neuroradiologists in consensus. OUTCOME MEASURES: The outcome measures were change in tumour size and pituitary hormone function. RESULTS: Sixty-six patients were managed conservatively for a mean follow-up period of 4·3 years (range: 1-14·7). Forty-seven (71%) had a macroadenoma, and nineteen (29%) had a microadenoma. Tumour size decreased or remained stable in 40% of macroadenomas and 47% of microadenomas. The median annual growth rate of enlarging macroadenomas and microadenomas was 1·0 mm/year and 0·4 mm/year, respectively. The median annual growth rate of macroadenomas was significantly higher than that of microadenomas (P < 0·01). Sixty-eight percentage of patients with a macroadenoma had pituitary hormone deficiency in one or more axes, compared to 42% of those with a microadenoma. CONCLUSION: Patients with NFPAs without optic chiasm compression can be managed conservatively. All patients need pituitary function assessment, irrespective of tumour size. These findings provide clinically relevant data for the management of patients with NFPAs.
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Adenoma/patología , Neoplasias Hipofisarias/patología , Adulto , Femenino , Humanos , Masculino , Hipófisis/patología , Estudios Retrospectivos , Espera VigilanteRESUMEN
A critical decision-step in the emergency treatment of ischemic stroke is whether or not to administer thrombolysis - a treatment that can result in good recovery, or deterioration due to symptomatic intracranial haemorrhage (SICH). Certain imaging features based upon early computerized tomography (CT), in combination with clinical variables, have been found to predict SICH, albeit with modest accuracy. In this proof-of-concept study, we determine whether machine learning of CT images can predict which patients receiving tPA will develop SICH as opposed to showing clinical improvement with no haemorrhage. Clinical records and CT brains of 116 acute ischemic stroke patients treated with intravenous thrombolysis were collected retrospectively (including 16 who developed SICH). The sample was split into training (n = 106) and test sets (n = 10), repeatedly for 1760 different combinations. CT brain images acted as inputs into a support vector machine (SVM), along with clinical severity. Performance of the SVM was compared with established prognostication tools (SEDAN and HAT scores; original, or after adaptation to our cohort). Predictive performance, assessed as area under receiver-operating-characteristic curve (AUC), of the SVM (0.744) compared favourably with that of prognostic scores (original and adapted versions: 0.626-0.720; p < 0.01). The SVM also identified 9 out of 16 SICHs, as opposed to 1-5 using prognostic scores, assuming a 10% SICH frequency (p < 0.001). In summary, machine learning methods applied to acute stroke CT images offer automation, and potentially improved performance, for prediction of SICH following thrombolysis. Larger-scale cohorts, and incorporation of advanced imaging, should be tested with such methods.
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Inteligencia Artificial , Encéfalo/diagnóstico por imagen , Fibrinolíticos/uso terapéutico , Evaluación de Resultado en la Atención de Salud , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Tomografía Computarizada por Rayos X , Área Bajo la Curva , Encéfalo/efectos de los fármacos , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Spoken language production is a complex brain function that relies on large-scale networks. These include domain-specific networks that mediate language-specific processes, as well as domain-general networks mediating top-down and bottom-up attentional control. Language control is thought to involve a left-lateralized fronto-temporal-parietal (FTP) system. However, these regions do not always activate for language tasks and similar regions have been implicated in nonlinguistic cognitive processes. These inconsistent findings suggest that either the left FTP is involved in multidomain cognitive control or that there are multiple spatially overlapping FTP systems. We present evidence from an fMRI study using multivariate analysis to identify spatiotemporal networks involved in spoken language production in humans. We compared spoken language production (Speech) with multiple baselines, counting (Count), nonverbal decision (Decision), and "rest," to pull apart the multiple partially overlapping networks that are involved in speech production. A left-lateralized FTP network was activated during Speech and deactivated during Count and nonverbal Decision trials, implicating it in cognitive control specific to sentential spoken language production. A mirror right-lateralized FTP network was activated in the Count and Decision trials, but not Speech. Importantly, a second overlapping left FTP network showed relative deactivation in Speech. These three networks, with distinct time courses, overlapped in the left parietal lobe. Contrary to the standard model of the left FTP as being dominant for speech, we revealed a more complex pattern within the left FTP, including at least two left FTP networks with competing functional roles, only one of which was activated in speech production.
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Encéfalo/fisiología , Cognición/fisiología , Red Nerviosa/fisiología , Habla/fisiología , Adulto , Anciano , Mapeo Encefálico , Femenino , Neuroimagen Funcional , Humanos , Lenguaje , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Percepción del Habla/fisiologíaRESUMEN
BACKGROUND: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. AIM: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. METHODS: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. RESULTS: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6 ± 0.4, vehicle; 5.0 ± 0.5, kisspeptin-54, P < .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P < .05 vs vehicle). CONCLUSIONS: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.
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Amenorrea/tratamiento farmacológico , Amenorrea/metabolismo , Enfermedades Hipotalámicas/tratamiento farmacológico , Enfermedades Hipotalámicas/metabolismo , Kisspeptinas/administración & dosificación , Hormona Luteinizante/metabolismo , Adolescente , Adulto , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Infusiones Intravenosas , Kisspeptinas/sangre , Hormona Luteinizante/sangre , Ciclo Menstrual/efectos de los fármacos , Ciclo Menstrual/metabolismo , Flujo Pulsátil/efectos de los fármacos , Adulto JovenAsunto(s)
Péptidos Cíclicos/efectos adversos , Síndrome de Leucoencefalopatía Posterior/inducido químicamente , alfa-MSH/análogos & derivados , Adulto , Femenino , Humanos , Inyecciones Subcutáneas , Imagen por Resonancia Magnética , Péptidos Cíclicos/administración & dosificación , Síndrome de Leucoencefalopatía Posterior/patología , Adulto Joven , alfa-MSH/administración & dosificación , alfa-MSH/efectos adversosRESUMEN
We report a 66-year-old man with a spinal, extradural solitary fibrous tumor showing unique retiform and papillary architecture. The patient presented in May 2008 with worsening right-sided lower back pain and urinary frequency. Magnetic resonance imaging of the spine documented a heterogeneously enhancing dumbbell-shaped extradural lesion causing cord compression at T11/12 level. The tumor extended to the paravertebral soft tissue and invaded the right adjacent vertebral pedicles and laminae. An angiogram showed prominent vascular supply mainly from the right T11 radicular artery. The patient underwent surgery to relieve cord compression in May 2008 and a second operation following embolization with coils in October 2009. No recurrence was observed at the last neuroimaging follow-up in June 2012. The tumor was composed of vimentin, CD34, Bcl-2, and CD99-positive rounded or slightly elongated cells with scant cytoplasm and oval to spindle nuclei. Several pseudovascular spaces reminiscent of the rete testis were present, and several of them contained papillary projections. Cytologic atypia was minimal, and mitotic activity was low. Focal infiltration of the paraspinal adipose tissue was seen at microscopic level. To our knowledge, retiform and papillary features have never been reported in a solitary fibrous tumor.
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Tumores Fibrosos Solitarios/patología , Neoplasias de la Columna Vertebral/patología , Antígeno 12E7 , Anciano , Angiografía , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Biomarcadores de Tumor/metabolismo , Moléculas de Adhesión Celular/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Tumores Fibrosos Solitarios/complicaciones , Tumores Fibrosos Solitarios/cirugía , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/patología , Compresión de la Médula Espinal/cirugía , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/cirugía , Resultado del TratamientoAsunto(s)
Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/terapia , Endarterectomía Carotidea/métodos , Angiografía por Resonancia Magnética/métodos , Ticlopidina/análogos & derivados , Enfermedades de las Arterias Carótidas/mortalidad , Arteria Carótida Común/diagnóstico por imagen , Arteria Carótida Común/patología , Clopidogrel , Endarterectomía Carotidea/efectos adversos , Endarterectomía Carotidea/mortalidad , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Seguridad del Paciente , Selección de Paciente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/fisiopatología , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/fisiopatología , Análisis de Supervivencia , Ticlopidina/uso terapéutico , Resultado del Tratamiento , Ultrasonografía Doppler Dúplex/métodos , Reino UnidoRESUMEN
There have been substantial advances in pituitary imaging in the last half-century. In particular, magnetic resonance imaging is now established as the imaging modality of choice, providing high quality images of the hypothalamic-pituitary axis and adjacent structures. More recent technological advances, such as the emergence of 3 Tesla MRI, are already being widely incorporated into imaging practice. However, other advanced techniques, including a variety of potential imaging biomarkers, still require further research to evaluate their potential and define their precise role. The recent development of intraoperative MRI appears promising and may have the potential to improve the outcome of pituitary surgery. Modern high quality imaging inevitably leads to the discovery of incidental lesions, including those within the pituitary gland, although it also plays a central role in their subsequent evaluation and management.
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Hipófisis/patología , Humanos , Imagen por Resonancia Magnética/métodos , Hipófisis/diagnóstico por imagen , RadiografíaRESUMEN
A 29-year-old Ethiopian man presented with marked bilateral visual loss, headache, hypopituitarism and significant hyponatraemia (115 mmol/L). A brain MRI scan demonstrated a large, lobulated, sellar and suprasellar mass, elevating the floor of the 3rd ventricle and compressing the optic chiasm. The patient underwent a transphenoidal resection of the mass followed by a craniotomy 10 days later. Histological examination demonstrated a Hyams' grade III neuroblastoma with ectopic expression of vasopressin. He underwent fractionated radiotherapy at a dose of 60 Gy in 30 fractions. Fourteen months after the onset, he is well with no neuroimaging evidence of tumour recurrence. His serum and urine sodium are completely normalised.
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Síndrome de Secreción Inadecuada de ADH/etiología , Neuroblastoma/complicaciones , Neoplasias Hipofisarias/complicaciones , Adulto , Humanos , Síndrome de Secreción Inadecuada de ADH/fisiopatología , Imagen por Resonancia Magnética , Masculino , Neuroblastoma/fisiopatología , Neoplasias Hipofisarias/fisiopatología , SíndromeRESUMEN
OBJECTIVE: Free-floating thrombus (FFT) of the carotid artery is a rare condition of currently unknown etiology. Less than 150 cases have been described in the published world literature to date. DESIGN AND SETTING: We present 6 consecutive cases of carotid FFT, identified prospectively from 5000 carotid duplex scans over a 34-month period in a single tertiary center for vascular surgery. RESULTS: All 6 cases involved the left carotid bifurcation in neurologically symptomatic individuals. In 5 of the 6 cases, FFT occurred in the absence of a significantly stenosing atheromatous plaque and was not associated with an elevation in velocity on duplex. The patients were all treated with surgical thromboendarterectomy, with good result. CONCLUSIONS: Duplex imaging can underestimate the degree of stenosis. Free-floating thrombus presents a challenge in diagnosis due to its rapidly evolving nature. The management of FFT by acute thromboendarterectomy appears to be safe and effective in limiting further focal neurological sequelae.
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Trombosis de las Arterias Carótidas/diagnóstico por imagen , Trombosis de las Arterias Carótidas/cirugía , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Endarterectomía Carotidea , Ultrasonografía Doppler Dúplex , Adulto , Anciano , Trombosis de las Arterias Carótidas/complicaciones , Estenosis Carotídea/complicaciones , Angiografía Cerebral/métodos , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Infarto de la Arteria Cerebral Media/etiología , Infarto de la Arteria Cerebral Media/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Ultrasonografía Doppler en Color , Adulto JovenRESUMEN
We report a case of primary leptomeningeal gliomatosis limited to the spinal cord occurring in a 52 years-old patient, who presented with back pain and leg weakness. MRI-scan of the craniospinal axis revealed an enhancing cervicothoracic lesion confined to the leptomeninges. A diagnostic biopsy was taken followed by a six level cervicothoracic laminoplasty with the aim of debulking of the dorsal portion of the tumour and relieving cord compression. Two weeks following surgery, the patient developed bilateral arm weakness. Repeat imaging revealed extension of the lesion to the level of the lower medulla. This patient underwent spinal radiotherapy and concomitant chemotherapy with Temozolomide, but she died of pneumonia 8.5 months after the time of diagnosis. No post-mortem was performed. Primary leptomeningeal gliomatosis exclusively involving the spinal cord is an extremely rare condition bearing a dismal prognosis. It can be suspected on neuroimaging, but histopathological examination is required for the final diagnosis. No current treatment protocols are available. Decompressive surgery may have a role in relieving symptoms, but no substantial benefit has been proven in administering radio-chemotherapy.
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Glioma/patología , Neoplasias Meníngeas/patología , Neoplasias de la Médula Espinal/patología , Femenino , Glioma/fisiopatología , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana EdadRESUMEN
BACKGROUND: Kisspeptin is a critical regulator of normal reproductive function. A single injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin release. However, the effects of kisspeptin on gonadotropin release in women with hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to humans are unknown. AIM: The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA. METHODS: We performed a prospective, randomized, double-blinded, parallel design study. Women with HA received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline (n = 5 per group) for 2 wk. Changes in serum gonadotropin and estradiol levels, LH pulsatility, and ultrasound measurements of reproductive activity were assessed. RESULTS: On the first injection day, potent increases in serum LH and FSH were observed after sc kisspeptin injection in women with HA (mean maximal increment from baseline within 4 h after injection: LH, 24.0 +/- 3.5 IU/liter; FSH, 9.1 +/- 2.5 IU/liter). These responses were significantly reduced on the 14th injection day (mean maximal increment from baseline within 4 h postinjection: LH, 2.5 +/- 2.2 IU/liter, P < 0.05; FSH, 0.5 +/- 0.5 IU/liter, P < 0.05). Subjects remained responsive to GnRH after kisspeptin treatment. No significant changes in LH pulsatility or ultrasound measurements of reproductive activity were observed. CONCLUSION: Acute administration of kisspeptin to women with infertility due to HA potently stimulates gonadotropin release, but chronic administration of kisspeptin results in desensitization to its effects on gonadotropin release. These data have important implications for the development of kisspeptin as a novel therapy for reproductive disorders in humans.