Delineation of Cohen syndrome following a large-scale genotype-phenotype screen

Cohen syndrome is an autosomal recessive condition associated with developmental delay, facial dysmorphism, pigmentary retinopathy, and neutropenia. The pleiotropic phenotype, combined with insufficient clinical data, often leads to an erroneous diagnosis and has led to confusion in the literature. Here, we report the results of a comprehensive genotype-phenotype study on the largest cohort of patients with Cohen syndrome assembled to date. We found 22 different COH1 mutations, of which 19 are novel, in probands identified by our diagnostic criteria. In addition, we identified another three novel mutations in patients with incomplete clinical data. By contrast, no COH1 mutations were found in patients with a provisional diagnosis of Cohen syndrome who did not fulfill the diagnostic criteria ("Cohen-like" syndrome). This study provides a molecular confirmation of the clinical phenotype associated with Cohen syndrome and provides a basis for laboratory screening that will be valuable in its diagnosis.     

Rare syndromes. The Kaufman-McKusick syndrome. A review of the 44 cases reported in the literature

The Kaufman-McKusick syndrome (MK 23670) is a rare autosomal recessive disorder characterized by the triad of hydrometrocolpos, postaxial polydactyly, and congenital heart disease. Multiple other anomalies have been ascribed to this syndrome. Hydrometrocolpos, especially if unrecognized, may be a serious, life-threatening condition in the newborn girl. Forty-four cases have been so far reported in the literature. A great phenotypic variability occurs in this syndrome, therefore making it very difficult to identify the disorder at its presentation and classify it correctly. We shall hereafter review current data regarding the prominent clinical features, the diagnosis and treatment of this syndrome. Problems in genetic counseling will be discussed.     

A rare association of hyperparathyroidism and Turner's syndrome--a case report

We present the clinical, laboratory, radiological and pathological findings in the case and review the literature. Our patient, a 37-year-old woman of short stature, was referred because of musculoskeletal pain. After primary evaluation, she underwent treatment with calcium and vitamin D supplement with the diagnosis of osteomalacia in Turner's syndrome. The rise of serum calcium during medical therapy, which was an unusual finding, attracted the clinician's attention to another underlying disorder. Further evaluation revealed primary hyperparathyroidism due to an adenoma of the parathyroid gland. Even though this is a rare diagnosis, its presence should be considered in any patient with Turner's syndrome presenting with severe osteoporosis and a rise in serum calcium during treatment.     

纳米材料在结核病诊疗中的应用

结核病是由结核分枝杆菌引起的慢性感染性疾病,经过呼吸道感染后侵犯机体器官,严重威胁全球公共卫生。传统结核诊疗手段存在诊断效率低、易误诊漏诊、易产生耐药、治疗效果和患者依从性差等瓶颈问题,亟需开发快速、准确的结核即时诊断（POC）方法和安全、高效的结核治疗方案,切实解决结核防治难题。本文总结了纳米材料在结核病诊疗领域的研究进展及应用前景,旨在为开发新一代安全、快速、有效的结核病诊疗方法提供参考。     

Personalized medicine using DNA biomarkers: a review

Biomarkers are of increasing importance for personalized medicine, with applications including diagnosis, prognosis, and selection of targeted therapies. Their use is extremely diverse, ranging from pharmacodynamics to treatment monitoring. Following a concise review of terminology, we provide examples and current applications of three broad categories of biomarkers-DNA biomarkers, DNA tumor biomarkers, and other general biomarkers. We outline clinical trial phases for identifying and validating diagnostic and prognostic biomarkers. Predictive biomarkers, more generally termed companion diagnostic tests predict treatment response in terms of efficacy and/or safety. We consider suitability of clinical trial designs for predictive biomarkers, including a detailed discussion of validation study designs, with emphasis on interpretation of study results. We specifically discuss the interpretability of treatment effects if a large set of DNA biomarker profiles is available and the number of therapies is identical to the number of different profiles.     

An APC for every occasion: induction and expansion of human Ag-specific CD4 and CD8 T cells using cellular and non-cellular APC

APC are used extensively to induce and expand Ag-specific T cells as well as to test their specificity and function. In the treatment of malignant and infectious diseases, APC are used to stimulate and expand Ag-specific T cells for adoptive transfer, or used directly in vivo to present Ag. The choice of APC to use depends on the particular application and on practical considerations, which include ease of production, availability, reproducibility and (for clinical use) established safety. The diversity of APC in use partly reflects the fact that no single technique of Ag presentation is ideal. For the clinician and laboratory worker alike the field can seem illogical and confusing. In this review we outline the functional requirements of APC for the induction of T cells, classify the APC in common use and describe their laboratory and clinical applications.     

Application of flow cytometry to the diagnosis of paroxysmal nocturnal hemoglobinuria

Within the contemporary multitude of complex methods used in clinical flow cytometry, very few techniques exist which can be described as disease-specific diagnostic tests. Detection of glycophosphatidylinositol (GPI)-linked antigens on hematopoietic cells using monoclonal antibodies and flow cytometry forms the basis of a specific diagnostic test for paroxysmal nocturnal hemoglobinuria (PNH). Absent or markedly diminished expression of GPI-linked antigens is, in the appropriate clinical setting, specific for all patients with PNH. Clinically, PNH is a syndrome characterized by bone marrow failure, acquired hemolytic anemia, and a thrombotic tendency. The molecular genetic lesion responsible for this condition is a somatic mutation of the X-linked pig-a gene within a multipotent hematopoietic stem cell. Due to its rarity, delay in diagnosis is not uncommon for patients with PNH. Once a definitive diagnosis is established, this can make a considerable impact on patient management and prognosis. In this article, we review the complimentary roles that molecular biology and flow cytometry have played in unraveling the genotypic and phenotypic aspects of this unique condition.     

Advances in the Diagnosis of Endemic Treponematoses: Yaws,Bejel, and Pinta

Improved understanding of the differential diagnosis of endemic treponematoses is needed to inform clinical practice and to ensure the best outcome for a new global initiative for the eradication of yaws, bejel, and pinta. Traditionally, the human treponematoses have been differentiated based upon their clinical manifestations and epidemiologic characteristics because the etiologic agents are indistinguishable in the laboratory. Serological tests are still considered standard laboratory methods for the diagnosis of endemic treponematoses and new rapid point-of-care treponemal tests have become available which are extremely useful in low-resource settings. In the past ten years, there has been an increasing effort to apply polymerase chain reaction to treponematoses and whole genome fingerprinting techniques have identified genetic signatures that can differentiate the existing treponemal strains; however, definitive diagnosis is also hampered by widespread unavailability of molecular diagnostics. We review the dilemmas in the diagnosis of endemic treponematoses, and advances in the discovery of new diagnostic tools.     

以中枢神经系统症状为首发表现的干燥综合征1例并文献复习

目的:探讨干燥综合征累及中枢神经病变的临床表现及诊断、鉴别诊断、治疗。方法:报告中国人民解放军第175医院1例累及中枢神经病变的干燥综合征患者的临床资料并复习相关文献,对其临床表现、诊断、容易混淆的鉴别诊断及治疗进行分析。结果:1例累及中枢神经病变的干燥综合征患者经治疗病情好转出院。结论:累及中枢神经病变的干燥综合征,尤其以中枢神经系统症状为首发表现者,极易误诊为多发性硬化,遇可疑病例应及时完善检查,避免因忽视其它系统症状而导致漏诊和误诊,影响患者的预后。     

Secondary psychoses: an update

Psychotic disorders due to a known medical illness or substance use are collectively termed secondary psychoses. In this paper, we first review the historic evolution of the concept of secondary versus primary psychosis and how this distinction supplanted the earlier misleading classification of psychoses into organic and functional. We then outline the clinical features and approach to the diagnosis of secondary psychotic disorders. Features such as atypical presentation, temporal relation to detectable medical cause, evidence of direct physiological causal relationship to the etiological agent, and the absence of evidence of a primary psychotic illness that may better explain the presentation suggest consideration of a secondary psychosis. Finally, we discuss how careful studies of secondary psychotic disorders can help elucidate the pathophysiology of primary, or idiopathic, psychotic disorders such as schizophrenia. We illustrate this issue through a discussion of three secondary psychotic disorders — psychoses associated with temporal lobe epilepsy, velocardiofacial syndrome, and N‐methyl D‐aspartate (NMDA) receptor encephalitis — that can, respectively, provide neuroanatomical, genetic, and neurochemical models of schizophrenia pathogenesis.     

Current scenario of COVID-19 in pediatric age group and physiology of immune and thymus response

COVID-19 pandemic caused by SARS-CoV-2, continues to manifest with severe acute respiratory syndrome among the adults, however, it offers a convincing indication of less severity and fatality in pediatric age group (0–18 years). The current trend suggests that children may get infected but are less symptomatic with less fatality, which is concordant to earlier epidemic outbreaks of SARS-CoV and MERS-CoV, in 2002 and 2012, respectively. According to the available data, children appear to be at lower risk for COVID-19, as adults constitute for maximum number of the confirmed cases (308,592) and deaths (13,069) as on 22nd March (https://www.worldometers.info/coronavirus). However, rapid publications and information of the adult patients with COVID-19 is in progress and published, on the contrary, almost no comprehensive data or discussion about the COVID-19 in children is available. Therefore, in this review, we outline the epidemiology, clinical symptoms, diagnosis, treatment, prevention, possible immune response and role of thymus in children to combat the COVID-19 outbreak.     

Bilateral Adrenalectomy: Lifesaving Procedure in Severe Cushing Syndrome

ObjectiveTo discuss the role of bilateral adrenalectomy in Cushing syndrome, as illustrated in a case of severe hypercortisolism that was unresponsive to combination agent medical therapy.MethodsWe report the clinical, laboratory, imaging, and pathologic findings in a patient with ectopic Cushing syndrome attributable to an adrenocorticotropic hormone (ACTH)-secreting neuroblastoma. In addition, we provide a literature review regarding olfactory neuroblastoma and discuss current and emerging therapeutic options for Cushing syndrome.ResultsA 59-year-old man presented with nasal congestion and neck swelling and was noted to have hypokalemia, hypertension, and hyperglycemia. A nasal biopsy demonstrated a poorly differentiated carcinoma with neuroendocrine features. He was subsequently diagnosed as having ACTH-dependent Cushing syndrome, but despite high-dose combination medical therapy, his condition rapidly deteriorated. Urgent bilateral adrenalectomy provided rapid control of the hypercortisolism, and the patient was later able to undergo an uncomplicated total macroscopic resection of his locally metastatic primary tumor.ConclusionThis report describes the challenges in the diagnosis and management of ACTH-dependent Cushing syndrome and highlights the important role that bilateral adrenalectomy can still have in patients with severe hypercortisolism causing life-threatening complications. (Endocr Pract. 2012;18:e85-e90)     

MicroRNAs and other small silencing RNAs in cancer

Small noncoding RNAs are key controllers of cellular function, and their deregulation can lead to cancer development and metastatic evolution. This review summarizes the most important examples of small RNAs involved in human cancer and discusses their clinical use as biomarkers and drug targets for diagnosis, prognosis, and treatment of cancer. We also describe the possible mechanisms underlying small RNA-mediated transformation and outline the future describing new small RNA families with great potential in cancer biology.     

临床生物化学与检验教育史话

临床生物化学与检验是在对人体正常、病理状况的生理生化变化过程认识的基础上,通过分析人体标本为疾病的诊断和治疗提供有用的信息。其课程主要内容包括糖类、脂类、核酸、蛋白质、酶、激素、有机小分子、血液气体、电解质、治疗性药物、临床毒物等的检测及其临床应用。临床生物化学与检验课程对临床医学和医学检验专业学生非常重要。本文对临床生物化学与检验课程建设的历史和现状进行了总结。     

Clinical and Laboratory Aspects of Insulin Autoantibody-Mediated Glycaemic Dysregulation and Hyperinsulinaemic Hypoglycaemia: Insulin Autoimmune Syndrome and Exogenous Insulin Antibody Syndrome

Autoimmune glycaemic dysregulation and hyperinsulinaemic hypoglycaemia mediated by insulin autoantibodies is an increasingly recognised but controversial phenomenon described in both exogenous insulin naïve (insulin autoimmune syndrome) and exposed (exogenous insulin antibody syndrome) individuals. There has been a significant proliferation of case reports, clinical studies and reviews in the medical literature in recent years which have collectively highlighted the discrepancy between experts in the field with regard to the nomenclature, definition, proposed pathophysiology, as well as the clinical and biochemical diagnostic criteria associated with the condition. The essential characteristics of the condition are glycaemic dysregulation manifesting as episodes of hyperglycaemia and unpredictable hyperinsulinaemic hypoglycaemia associated with high titres of endogenous antibodies to insulin. Although the hypoglycaemia is often life-threatening and initiation of targeted therapies critical, the diagnosis is often delayed and attributable to various factors including: the fact that existence of the condition is not universally accepted; the need to exclude surreptitious causes of hypoglycaemia; the diverse and often complex nature of the glycaemic dysregulation; and the challenge of diagnostic confirmation. Once confirmed, the available therapeutic options are expansive and the reported responses to these therapies have been variable. This review will focus on our evolving understanding, and the associated diagnostic challenges – both clinical and laboratory – of this complex condition.     

Molecular targets in immune-mediated diseases: the case of tumour necrosis factor and rheumatoid arthritis

Rheumatoid arthritis is a common autoimmune condition in which, for unknown reasons, synovial joints become the target of a sustained immune response. For many years, rheumatoid arthritis was in the 'too hard basket' in terms of understanding disease mechanisms and providing rational therapy. This has changed dramatically over the last 10 years and rheumatoid arthritis is now at the forefront of biotechnology. In this review, we outline one of the most exciting recent developments, namely antagonists of the cytokine TNF. The preclinical evaluation of TNF in animal models of rheumatoid arthritis, and subsequent clinical trials of TNF inhibitors in patients, provides insight into the 'bench to bedside' paradigm. We therefore briefly review rheumatoid arthritis, animal models of rheumatoid arthritis, the biology of TNF, the pivotal clinical trials of TNF antagonists and the emerging data on side-effects. Tumour necrosis factor inhibitors in rheumatoid arthritis represent the first attempt to achieve sustained blockade of a single cytokine in a human disease. Whilst this approach has been even more successful than might have been predicted, we suggest it is only the beginning of what has become a new therapeutic era.     

Sheehan Syndrome Presenting as Central Diabetes Insipidus: A Rare Presentation of an Uncommon Disorder

ObjectiveTo add to the current scant literature on rare clinical presentations of Sheehan syndrome.MethodsWe describe the study patient’s clinical, laboratory, and imaging findings and review the literature for publications regarding varied clinical presentations of Sheehan syndrome.ResultsA 36-year-old multigravida woman developed severe postpartum hemorrhage and disseminated intravascular coagulation followed by Sheehan syndrome, with central diabetes insipidus as the primary presenting feature. This was diagnosed when, postoperatively, she developed polyuria with a urine output of 11 L in 24 hours with an accompanying rise in creatinine. She had laboratory evidence of diabetes insipidus, with serum osmolality greater than urine osmolality. Her clinical status improved significantly with intranasal desmopressin supplementation, thus confirming the diagnosis of Sheehan syndrome. Although Sheehan syndrome is a known complication of postpartum hemorrhage, central diabetes insipidus is seldom considered or suspected. Hypovolemia is usually presumed to be secondary to blood loss and polyuria resulting from a diuretic phase of acute renal failure.ConclusionsIt is important to consider posterior pituitary ischemia resulting from Sheehan syndrome presenting as central diabetes insipidus as a cause of polyuria because appropriate hormonal replacement initiated early can possibly improve clinical status and patient outcomes. (Endocr Pract. 2011;17:108-114)     

Is ADHD a valid diagnosis in older adults?

ADHD is a neurodevelopmental syndrome that often persists into adulthood. It is possible that different criteria are necessary for older adults than younger adults: the manifestations of ADHD could change with age; other conditions with onset in later life share presenting symptoms with ADHD; different contextual challenges and patterns of compensatory support may exist. For these reasons, we reviewed evidence for the validity of DSM ADHD criteria in adulthood for individuals over the age of 50. Specifically, we evaluated evidence that the DSM criteria for ADHD identify a valid syndrome in older adults based on clinical presentation, laboratory or testing findings, absence of alternate diagnosis to explain symptoms, course of the syndrome, or familial presence of the condition. We found evidence that various ADHD criteria identify subjects with clinical presentations similar to that seen in younger adults, but only 92 well-described cases have been reported in the literature. ADHD traits also may be less common in the general population of older adults than in younger adults, suggesting that the threshold for an atypical burden of ADHD traits may be lower in older populations. Future research can establish a richer basis for validity of diagnostic criteria for ADHD in older adults.     

Serum autoantibodies profiling and early-stage cancer detection

It is now well established that an immune response to cancer is elicited in humans, as demonstrated in part by the identification of autoantibodies against a number of tumor-associated antigens in sera from patients with different types of cancer. During these past few years, proteomic approaches have been developed to identify tumor-associated antigens and their cognate autoantibodies. Detection of a panel of serum autoantibodies has thus been proposed as a new method for early cancer diagnosis. Early detection seems to be particularly adequate in high-risk populations, such as heavy smokers for lung cancer or in women with high mammographic density for breast cancer. In this review, we highlight the features of serum autoantibody biomarkers and outline the proteomic strategies employed to identify and validate their use in clinical practice for cancer screening and diagnosis. We particularly emphasize the clinical utility of autoantibody signatures, using the examples of lung and breast cancer. Finally, we discuss the challenges remaining for clinical validation.