Clinicopathologic correlations of silent corticotroph adenomas of the pituitary: report of four cases and literature review

Silent corticotroph adenomas (SCA) are rare pituitary tumors with histologic hallmarks of corticotroph differentiation, including ACTH immunoreactivity, but lacking clinical evidence of Cushing's syndrome. We report on four female patients, aged 19-66 years, each presenting with a nonfunctional macroadenoma. Leading symptoms were headache in two cases and visual field deficits in one. One patient was incidentally diagnosed while undergoing cranial MRI for an unrelated condition. Three patients had marked obesity; none of them presented constitutional signs of Cushing's syndrome. Serum cortisol levels were moderately elevated in the two patients systematically tested in this respect. Marginal to moderate hyperprolactinemia was present in two cases. Two patients also were shown to be deficient in either gonadotroph or thyrotroph axis, while a third had a combined insufficiency of both gonadotroph and thyrotroph axis. MRI scans revealed intratumoral hemorrhage and/or cystic change in three cases, as well as tumor-related occlusive hydrocephalus in one. The latter patient was biopsied only, while the remaining underwent gross total resection. Histologically, all four lesions were diagnosed as SCA subtype I displaying intense immunoreactivity for ACTH. In three tumors, scattered cells coexpressed PRL as well. In addition, Crooke's hyaline change was noted in a significant number of tumor cells and in residual non-neoplastic corticotrophs in one case each. With MIB-1 labeling indices of 1-3%, none of the tumors qualified as atypical adenoma. We conclude that SCAs are more likely to be discovered as expansile tumors, whose advanced local space-occupying character at surgery rather than an inherently aggressive growth potential may negatively influence the clinical outcome. Subtle morphologic evidence of corticotroph suppression in residual pituitary adjacent to tumor lends further support to literature data indicating minimal or intermittent functional activity in this tumor type.

Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice

BACKGROUND: Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. METHODS: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. RESULTS: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. CONCLUSIONS: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.

The European Court of Justice and process-oriented review. Research Paper in Law, 01/2012

Structuralism is a theory of U.S. constitutional adjudication according to which courts should seek to improve the decision-making process of the political branches of government so as to render it more democratic.1 In words of John Hart Ely, courts should exercise their judicial-review powers as a ‘representation-reinforcing’ mechanism.2 Structuralism advocates that courts must eliminate the elements of the political decision-making process that are at odds with the structure set out by the authors of the U.S. Constitution. The advantage of this approach, U.S. scholars posit, lies in the fact that it does not require courts to second-guess the policy decisions adopted by the political branches of government. Instead, they limit themselves to enforcing the constitutional structure within which those decisions must be adopted. Of course, this theory of constitutional adjudication, like all theories, has its shortcomings. For example, detractors of structuralism argue that it is difficult, if not impossible, to draw the dividing line between ‘substantive’ and ‘structural’ matters.3 In particular, they claim that, when identifying the ‘structure’ set out by the authors of the U.S. Constitution, courts necessarily base their determinations not on purely structural principles, but on a set of substantive values, evaluating concepts such as democracy, liberty and equality. 4 Without claiming that structuralism should be embraced by the ECJ as the leading theory of judicial review, the purpose of my contribution is to explore how recent case-law reveals that the ECJ has also striven to develop guiding principles which aim to improve the way in which the political institutions of the EU adopt their decisions. In those cases, the ECJ decided not to second-guess the appropriateness of the policy choices made by the EU legislator. Instead, it preferred to examine whether, in reaching an outcome, the EU political institutions had followed the procedural steps mandated by the authors of the Treaties. Stated simply, I argue that judicial deference in relation to ‘substantive outcomes’ has been counterbalanced by a strict ‘process review’. To that effect, I would like to discuss three recent rulings of the ECJ, delivered after the entry into force of the Treaty of Lisbon, where an EU policy measure was challenged indirectly, i.e. via the preliminary reference procedure, namely Vodafone, Volker und Markus Schecke and Test-Achats.5 Whilst in the former case the ECJ ruled that the questions raised by the referring court disclosed no factor of such a kind as to affect the validity of the challenged act, in the latter cases the challenged provisions of an EU act were declared invalid.

The Silent Reform of Swiss Federalism: The New Constitutional Articles on Education

This article examines the decision-making process leading to the new constitutional articles on education in Switzerland. It analyzes how actors from both state levels (Confederation and cantons) could reach consensus in a process that was prone to a "joint-decision trap". To that end, we hypothesize which factors may be conducive to a "problem-solving" style of policy-making in a compulsory negotiation system. Rich empirical material from various sources supports our theoretical arguments: We show that shared beliefs and a common frame of reference, the procedural separation between constitutional and distributional issues, neutral brokers, and informal structures were all beneficial to the success of the reform project.

Review of a report to the House of Representatives of the Commonwealth of Massachusetts, on the case of William Vans. With observations upon the dispensing power of the Legislature, and upon a decision of the Supreme Judicial Court, "nullifying" the said power.

"Postscript by William Vans": p. [13]-15 at end.

Review of a pamphlet on the trust deed of the Hanover Church.

The Boston Athenaeum, in its Catalogue, suggests Lyman Beecher as possible author. Richard H. Shoemaker's A checklist of American imprints for 1828 mentions Beecher and Benjamin Wisner as possible authors.

Judicial Impartiality and Independence in Divided Societies: An Empirical Analysis of the Constitutional Court of Bosnia-Herzegovina

The role of Constitutional Courts in deeply divided societies is complicated by the danger that the salient societal cleavages may influence judicial decision-making and, consequently, undermine judicial independence and impartiality. With reference to the decisions of the Constitutional Court of Bosnia-Herzegovina, this article investigates the influence of ethno-nationalism on judicial behaviour and the extent to which variation in judicial tenure amplifies or dampens that influence. Based on a statistical analysis of an original dataset of the Court’s decisions, we find that the judges do in fact divide predictably along ethno-national lines, at least in certain types of cases, and that these divisions cannot be reduced to a residual loyalty to their appointing political parties. Contrary to some theoretical expectations, however, we find that long-term tenure does little to dampen the influence of ethno-nationalism on judicial behaviour. Moreover, our findings suggest that the longer a judge serves on the Court the more ethno-national affiliation seems to influence her decision-making. We conclude by considering how alternative arrangements for the selection and tenure of judges might help to ameliorate this problem.

Expanding our Constitutional Horizons: A Comprehensive Study of Quasi-Constitutionality in Canada

A number of laws in Canada which uphold rights are referred to as quasi-constitutional by the courts in recognition of their special importance. Quasi-constitutional statutes are enacted through the regular legislative process, although they are being interpreted and applied in a fashion which has become remarkably similar to constitutional law, and are therefore having an important affect over other legislation. Quasi-constitutionality has surprisingly received limited scholarly attention, and very few serious attempts at explaining its significance have been made. This dissertation undertakes a comprehensive study of quasi-constitutionality which considers its theoretical basis, its interpretation and legal significance, as well as its similarities to comparable forms of law in other Commonwealth jurisdictions. Part I examines the theoretical basis of quasi-constitutionality and its relationship to the Constitution. As a statutory and common law form of fundamental law, quasi-constitutionality is shown to signify an association with the Canadian Constitution and the foundational principles that underpin it. Part II proceeds to consider the special rules of interpretation applied to quasi-constitutional legislation, the basis of this interpretative approach, and the connection between the interpretation of similar provisions in quasi-constitutional legislation and the Constitution. As a statutory form of fundamental law, quasi-constitutional legislation is given a broad, liberal and purposive interpretation which significantly expands the rights which they protect. The theoretical basis of this approach is found in both the fundamental nature of the rights upheld by quasi-constitutional legislation as well as legislative intent. Part III explores how quasi-constitutional statutes affect the interpretation of regular legislation and how they are used for the purposes of judicial review. Quasi-constitutional legislation has a significant influence over regular statutes in the interpretative exercise, which in some instances results in conflicting statutes being declared inoperable. The basis of this form of judicial review is demonstrated to be rooted in statutory interpretation, and as such it provides an interesting model of rights protection and judicial review that is not conflated to constitutional and judicial supremacy.

Bisphosphonate-related Osteonecrosis Of The Jaw: A Review Of The Literature.

Bisphosphonates (BPs) are a class of drugs used to treat osteoporosis and malignant bone metastasis. BPs show high binding capacity to the bone matrix, especially in sites of active bone metabolism. The American Society for Bone and Mineral Research defines BRONJ as an area of exposed bone in the maxillofacial region that has not healed within 8 weeks after identification by a healthcare provider in a patient who is receiving or has been exposed to a bisphosphonate and has not had radiation therapy to the craniofacial region. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) can adversely affect quality of life, as it may produce significant morbidity. The American Association of Oral and Maxillofacial Surgeons (AAOMS) considers as vitally important that information on BRONJ be disseminated to other dental and medical specialties. The purpose of this work is to offer a perspective on how dentists should manage patients on BPs, to show the benefits of accurately diagnosing BRONJ, and to present diagnostic aids and treatments strategies for the condition.

Health-related And Socio-demographic Factors Associated With Frailty In The Elderly: A Systematic Literature Review.

Frailty is a syndrome that leads to practical harm in the lives of elders, since it is related to increased risk of dependency, falls, hospitalization, institutionalization, and death. The objective of this systematic review was to identify the socio-demographic, psycho-behavioral, health-related, nutritional, and lifestyle factors associated with frailty in the elderly. A total of 4,183 studies published from 2001 to 2013 were detected in the databases, and 182 complete articles were selected. After a comprehensive reading and application of selection criteria, 35 eligible articles remained for analysis. The main factors associated with frailty were: age, female gender, black race/color, schooling, income, cardiovascular diseases, number of comorbidities/diseases, functional incapacity, poor self-rated health, depressive symptoms, cognitive function, body mass index, smoking, and alcohol use. Knowledge of the complexity of determinants of frailty can assist the formulation of measures for prevention and early intervention, thereby contributing to better quality of life for the elderly.

Interface Between Intellectual Disability And Mental Health: Hermeneutic Review.

A literature review was conducted aiming to understand the interface between the Intellectual Disability and Mental Health fields and to contribute to mitigating the path of institutionalizing individuals with intellectual deficiencies. The so-called dual diagnosis phenomenon remains underestimated in Brazil but is the object of research and specific public policy internationally. This phenomenon alerts us to the prevalence of mental health problems in those with intellectual disabilities, limiting their social inclusion. The findings reinforce the importance of this theme and indicate possible diagnostic invisibility of the development of mental illness in those with intellectual disabilities in Brazil, which may contribute to sustaining psychiatric institutionalization of this population. 

Cervical Spine Involvement In Rheumatoid Arthritis--a Systematic Review.

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disorder that can compromise the cervical spine in up to 80% of the cases. The most common radiological presentations of cervical involvement are atlantoaxial subluxation (AAS), cranial settling and subaxial subluxation (SAS). We performed a systematic review in the PubMed Database of articles published later 2005 to evaluate the prevalence, progression and risk factors for cervical spine involvement in RA patients. Articles were classified according to their level of evidence. Our literature review reported a wide range in the prevalence of cervical spine disease, probably explained by the different studied populations and disease characteristics. Uncontrolled RA is probably the main risk factor for developing a spinal instability. Adequate treatment with DMARD and BA can prevent development of cervical instabilities but did not avoid progression of a pre-existing injury. MRI is the best radiological method for diagnosis cervical spine involvement. AAS is the most common form of RA. Long term radiological follow-up is necessary to diagnosis patients with late instabilities and monitoring progression of diagnosed injuries.

[recommendations For Physical Exercise Practice During Pregnancy: A Critical Review].

Physical exercise is recommended for all healthy pregnant women. Regular practice of exercises during pregnancy can provide many physical and psychological benefits, with no evidence of adverse outcomes for the fetus or the newborn when exercise is performed at mild to moderate intensity. However, few pregnant women engage in this practice and many still have fears and doubts about the safety of exercise. The objective of the present study was to inform the professionals who provide care for Brazilian pregnant women about the current recommendations regarding physical exercise during pregnancy based on the best scientific evidence available. In view of the perception that few systematic models are available about this topic and after performing several studies in this specific area, we assembled practical information of interest to both the professionals and the pregnant women. We also provide recommendations about the indications, contraindications, modalities (aerobics, resistance training, stretching and pelvic floor training), frequency, intensity and duration indicated for each gestational trimester. The review addresses physical exercise recommendation both for low risk pregnant women and for special populations, such as athletes and obese, hypertensive and diabetic subjects. The advantages of an active and healthy lifestyle should be always reinforced during and after gestation since pregnancy is an appropriate period to introduce new habits because pregnant women are usually more motivated to adhere to recommendations. Thus, routine exams, frequent returns and supervision are recommended in order to provide new guidelines that will have long-term beneficial effects for both mother and child.

Management Of Severe Thoracic Impalement Trauma Against Two-wheeled Horse Carriage: A Case Report And Literature Review.

Thoracic injuries in general are of great importance due to their high incidence and high mortality. Thoracic impalement injuries are rare but severe due to the combination of cause, effect and result. This study's primary objective is to report the case of a young man who was impaled by a two-wheeled horse carriage shaft while crashing his motorcycle in a rural zone. An EMT-B ferry was called at the crash scene and a conscious patient was found, sustaining a severe impalement injury to the left hemithorax, suspended over the floor by the axial skeleton with the carriage shaft coming across his left chest. As a secondary objective, a literature review of thoracic impalement injuries is performed. Cases of thoracic impalement injury require unique and individualized care based on injury severity and affected organs. Reported protocols for managing impalement injuries are entirely anecdotal, with no uniformity on impaled patient's approach and management. In penetrating trauma, it is essential not to remove the impaled object, so that possible vascular lesions remain buffered by the object, avoiding major bleeding and exsanguination haemorrhage. Severed impaled thoracic patients should be transferred to a specialist centre for trauma care, as these lesions typically require complex multidisciplinary treatment. High-energy thoracic impalement injuries are rare and hold a high mortality rate, due to the complexity of trauma and associated injuries such as thoracic wall and lung lesions. Modern medicine still seems limited in cases of such seriousness, not always with satisfactory results.

Influence Of Cyclosporine On The Occurrence Of Nephrotoxicity After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review.

Cyclosporine, a drug used in immunosuppression protocols for hematopoietic stem cell transplantation that has a narrow therapeutic index, may cause various adverse reactions, including nephrotoxicity. This has a direct clinical impact on the patient. This study aims to summarize available evidence in the scientific literature on the use of cyclosporine in respect to its risk factor for the development of nephrotoxicity in patients submitted to hematopoietic stem cell transplantation. A systematic review was made with the following electronic databases: PubMed, Web of Science, Embase, Scopus, CINAHL, LILACS, SciELO and Cochrane BVS. The keywords used were: bone marrow transplantation OR stem cell transplantation OR grafting, bone marrow AND cyclosporine OR cyclosporin OR risk factors AND acute kidney injury OR acute kidney injuries OR acute renal failure OR acute renal failures OR nephrotoxicity. The level of scientific evidence of the studies was classified according to the Oxford Centre for Evidence Based Medicine. The final sample was composed of 19 studies, most of which (89.5%) had an observational design, evidence level 2B and pointed to an incidence of nephrotoxicity above 30%. The available evidence, considered as good quality and appropriate for the analyzed event, indicates that cyclosporine represents a risk factor for the occurrence of nephrotoxicity, particularly when combined with amphotericin B or aminoglycosides, agents commonly used in hematopoietic stem cell transplantation recipients.