Great Ormond Street Hospital

About: Great Ormond Street Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Transplantation & Population. The organization has 6535 authors who have published 11240 publications receiving 413647 citations. The organization is also known as: GOSH & Hospital for Sick Children.

Failure of Stroke Volume Augmentation During Exercise and Dobutamine Stress Is Unrelated to Load-Independent Indexes of Right Ventricular Performance After the Mustard Operation

Abstract: Background—Impaired right ventricular function has been implicated as a cause of reduced maximal exercise capacity after the Mustard operation for transposition of the great arteries. Methods and Results—Fourteen asymptomatic survivors of the Mustard operation were studied. Each underwent conventional cardiac catheterization, and after satisfactory hemodynamics were confirmed, load-independent indexes of ventricular function were derived by conductance catheter during dobutamine infusion (0, 5, and 10 μg · kg−1 · min−1). Seven patients also underwent upright exercise testing on a bicycle ergometer with analysis of respiratory gas exchange by continuous mass spectrometry. Accessible pulmonary blood flow was measured at each workload with an automated acetylene rebreathing technique. All patients exercised to a satisfactory end point (respiratory quotient >1.1). Maximum oxygen consumption during exercise was impaired compared with predicted values (mean, 77%; P<0.02). Both exercise and dobutamine infusion w...

Quantification of bolus-tracking MRI: Improved characterization of the tissue residue function using Tikhonov regularization.

Abstract: Quantification of cerebral blood flow (CBF) and the tissue residue function (R) using bolus-tracking MRI requires deconvolution of the arterial input function (AIF). Currently, the most commonly used deconvolution method is singular value decomposition (SVD), which has been shown to produce accurate estimations of CBF. However, this method introduces unwanted oscillations in the time course of R, and there are situations in which the actual shape is of interest (e.g., in calculating flow heterogeneity and assessing bolus dispersion). In such cases, the conventional SVD method may no longer be suitable, and an alternative approach may be required. This work describes the implementation of Tikhonov regularization with the L-curve criterion to quantify CBF and obtain a better characterization of R. The methodology is tested on simulated and patient data, and the results are compared to those found using the conventional SVD approach. Although both methods produce similar CBF values, the deconvolved R shape obtained using SVD is dominated by oscillations and fails to characterize the shape in the presence of dispersion. On the other hand, the use of the proposed regularization method improves the characterization of the tissue residue function.

Molecular and developmental mechanisms of anterior segment dysgenesis

Abstract: Anterior segment dysgenesis (ASD) is a failure of the normal development of the tissues of the anterior segment of the eye. It leads to anomalies in the structure of the mature anterior segment, associated with an increased risk of glaucoma and corneal opacity. Several different gene mutations have been identified underlying these anomalies with the majority of ASD genes encoding transcriptional regulators. In this review, the role of the ASD genes, PITX2 and FOXC1, is considered in relation to the embryology of the anterior segment, the biochemical function of these proteins, and their role in development and disease aetiology. The emerging view is that these genes act in concert to specify a population of mesenchymal progenitor cells, mainly of neural crest origin, as they migrate anteriorly around the embryonic optic cup. These same genes then regulate mesenchymal cell differentiation to give rise to distinct anterior segment tissues. Development appears critically sensitive to gene dosage, and variation in the normal level of transcription factor activity causes a range of anterior segment anomalies. Interplay between PITX2 and FOXC1 in the development of different anterior segment tissues may partly explain the phenotypic variability and the genetic heterogeneity characteristic of ASD.

Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

Abstract: Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.