An Update on Glomerulopathies

An Update on Glomerulopathies - Clinical and Treatment Aspects is a systemic overview of recent advances in clinical aspects and therapeutic options in major syndromes of glomerular pathology. The book contains twenty four chapters divided conveniently into five sections. The first section deals with primary glomerulopathies, and the second section is devoted to glomerulopathies complicating infectious conditions. The third section deals with systemic autoimmune disorders and vasculitides which constitute major causes of glomerular disease and often renal failure. The fourth section includes chapters discussing the glomerular involvement in some major metabolic and systemic conditions. The final section has chapters which relate to some general aspects of glomerular diseases. This book will form an excellent reference tool for practicing and academic nephrology community

Effects of Cyclosporin A Therapy Combined with Steroids and Angiotensin Converting Enzyme Inhibitors on Childhood IgA Nephropathy

To evaluate the effects of cyclosporin A (CyA) on clinical outcome and pathologic changes in children with IgA nephropathy (IgAN), we retrospectively evaluated 14 children (mean age 8.9±2.9 yr; eight males, six females) who were treated with CyA and steroids. The starting dose of CyA was 5 mg/kg per day, and the drug level was maintained at 100-200 ng/mL. The mean CyA level was 183.8±48.3 ng/mL (range 120.7-276.0 ng/mL) and the mean duration of CyA therapy was 10.9±1.9 months (range 8-12 months). After CyA therapy the mean 24 hr urinary protein excretion declined from 107.1±35.1 mg/m2/hr to 7.4±2.4 mg/m2/hr (P<0.001) and serum albumin increased from 3.3±0.6 g/dL to 4.3±0.3 g/dL (P<0.001). At a follow-up biopsy the histological grade of IgAN was improved in seven (50%) of the 14 patients, remained the same in three (21%), and was aggravated in four (29%). Serum creatinine, creatinine clearance, and blood pressure did not differ before and after CyA therapy. Two patients (14%) showed CyA-induced nephrotoxicity at the second biopsy. Our findings indicate that CyA therapy may be effective in reducing proteinuria and regressing renal pathology in a subset of children with IgAN

Skills in Rheumatology

This Open Access book presents practical approaches to managing patients affected by various rheumatological diseases, allowing readers to gain a better understanding of the various clinical expressions and problems experienced by these patients. Discussing rheumatology from an organ systems perspective, it highlights the importance ofdetailed musculoskeletal examinations when treating patients affected by rheumatological diseases. The book first explores the latest diagnostic approaches and offers key tips for accurate musculoskeletal examinations before addressing the various treatment modalities, with a particular focus on the most common joints involved in rheumatoid arthritis: the wrists and the metacarpophalangeal joints (2nd and 3rd). Featuring easy-to-understand flow diagrams and explaining the common medical problems associated with rheumatic disease, such as shortness of breath and anemia, it is not only a valuable resource to rheumatologists, but will also appeal to medical students, junior residents, and primary healthcare physicians

Novel Genetic Causes of Cerebral and Systemic Vasculopathies

Vasculopathies are a varied group of disorders that affect the vascular tree resulting in arterial stenosis or dilatation causing multi-organ ischaemia and significant cardiac and cerebral circulation complications. Commonly, vasculopathies present in infancy and segregate within families so a genetic cause is often suspected but not always identified by the current routinely available genetic tests in the UK National Health Service (NHS). Due to the overlapping phenotypes of these disorders genetic sequencing is required for accurate diagnosis and appropriate clinical intervention. In this thesis, a cohort of children with cerebral and systemic vasculopathies was subject to next-generation genetic sequencing. Several discoveries were made and various families are discussed herein. Firstly, a novel heterozygous mutation in MYH11, a gene affecting smooth muscle myosin heavy chain, was identified in a child with a moyamoya-like cerebrovascular disease and renal artery stenosis. This expanded the vasculopathic phenotype associated with MYH11, which previously was associated with familial aortopathy. Secondly, multiple members of three families diagnosed with a moyamoya arteriopathy were studied and were all found to have heterozygous mutations in c-CBL, an E3 ubiquitin ligase that down regulates various receptor tyrosine kinases. Detailed in vitro functional expression studies were undertaken in the patients with mutations in c-CBL showing impaired CBL-mediated degradation of cell-surface receptors in a dominant negative fashion. These results were compatible with dysregulated intracellular signaling through RAS. Lastly, three families with systemic vasculopathies associated with heterozygous mutations in RNF213 were also studied. This protein possesses both ubiquitin ligase and ATPase activity and adversely affects endothelial cell function. For the first time I showed that heterozygous mutations in RNF213 cause a vasculopathy that is not confined to the cerebral circulation

Skills in Rheumatology

This Open Access book presents practical approaches to managing patients affected by various rheumatological diseases, allowing readers to gain a better understanding of the various clinical expressions and problems experienced by these patients. Discussing rheumatology from an organ systems perspective, it highlights the importance ofdetailed musculoskeletal examinations when treating patients affected by rheumatological diseases. The book first explores the latest diagnostic approaches and offers key tips for accurate musculoskeletal examinations before addressing the various treatment modalities, with a particular focus on the most common joints involved in rheumatoid arthritis: the wrists and the metacarpophalangeal joints (2nd and 3rd). Featuring easy-to-understand flow diagrams and explaining the common medical problems associated with rheumatic disease, such as shortness of breath and anemia, it is not only a valuable resource to rheumatologists, but will also appeal to medical students, junior residents, and primary healthcare physicians

Glomerular and tubular proteome markers of progressive IgA nephropathy

Background: IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, with a clinical course ranging from asymptomatic non-progressive to aggressive and progressive disease to kidney failure. The exact mechanism of progression is not fully understood and further research is needed. Proteomics could help to investigate the mechanism of progression in IgAN and define potential biomarkers. The aims of this study were: -To identify novel tissue biomarkers for progressive IgAN that may be used for prognostication. -To improve understanding of underlying mechanisms in IgAN. -To separately investigate glomerular and tubular biomarkers in IgAN. Methods: Formalin-fixed paraffin-embedded kidney biopsy of patients with IgAN and control from the Norwegian Kidney Biopsy Registry were used. The IgAN group was divided in progressive or non-progressive based on progression to kidney failure over 10 years. Glomerular and tubulointerstitial tissues were microdissected, the proteome was analysed using mass spectrometry and the protein abundance was compared between groups. Results: As compared to IgAN patients without progressive disease, glomeruli from patients with progressive IgAN had significantly higher abundance of components of the classical and the terminal complement pathways (Paper I), and the tubulointerstitial tissue had higher abundance of proteins related to inflammation (Paper III). As compared to controls, glomeruli from patients with IgAN showed significantly higher abundance of extracellular matrix structural proteins and extracellular matrix associated proteins (Paper II). Periostin was the protein with the highest fold change between groups both in glomeruli and tubuli. Conclusions: Microdissection of glomeruli and tubuli allowed for compartment-specific analyses of prognostic markers and a better understanding of underlying mechanisms of progressive IgAN. The most promising marker seem to be periostin which associated with progressive disease both in glomeruli and tubuli.Doktorgradsavhandlin

Urinary Tract Infection and Nephropathy

In this book, experts from different countries demonstrate clinical and research advances in nephropathy and urinary tract infection (UTI). Chapters cover such topics as membranous nephropathy, diabetic nephropathy, multidrug resistance in UTI, pathogens and bacteria associated with UTI, and more

New Techniques in Gastrointestinal Endoscopy

As result of progress, endoscopy has became more complex, using more sophisticated devices and has claimed a special form. In this moment, the gastroenterologist performing endoscopy has to be an expert in macroscopic view of the lesions in the gut, with good skills for using standard endoscopes, with good experience in ultrasound (for performing endoscopic ultrasound), with pathology experience for confocal examination. It is compulsory to get experience and to have patience and attention for the follow-up of thousands of images transmitted during capsule endoscopy or to have knowledge in physics necessary for autofluorescence imaging endoscopy. Therefore, the idea of an endoscopist has changed. Examinations mentioned need a special formation, a superior level of instruction, accessible to those who have already gained enough experience in basic diagnostic endoscopy. This is the reason for what these new issues of endoscopy are presented in this book of New techniques in Gastrointestinal Endoscopy

Endothelial injury and repair in childhood arterial ischaemic stroke

Abnormalities of the cervical or intracranial circulation, termed arteriopathies are the leading mechanism of both cause and recurrence of childhood arterial ischaemic stroke (AIS). Approximately 20% of children with AIS will have stroke recurrence but there are currently no robust biomarkers to identify this high risk group, and hence identification of patients who may be amenable to secondary preventative strategies has not been possible. This thesis attempts to address this unmet need by studying novel biomarkers to distinguish patients at risk of stroke recurrence. Indices of endothelial injury, repair and hypercoagulability were compared between patients with recurrent clinical disease course and children with a single event. Circulating endothelial cells (CECs) were higher in children with recurrent AIS, compared to those with no recurrence and controls. Further evidence of endothelial injury and cellular activation was derived by examining circulating microparticles (MP) profiles. Plasma from patients with AIS recurrence contained increased numbers of endothelial, platelet and neutrophil derived MP compared to those with no recurrence. These MPs were highly prothrombotic due to phosphatidylserine exposure providing a platform for the assembly and activation of coagulation factors; and also expression of tissue factor on some MP. An efficient in vitro assay to assess MP-related hypercoagulability by quantifying MP-mediated thrombin generation was established. Children with recurrent AIS were shown to have an enhanced MP-mediated thrombin generation. Lastly, a disturbance in endothelial progenitor cells (EPCs) in children with AIS recurrence was observed suggesting that there could be impairment of endothelial repair in these patients. In conclusion, despite the wide spectrum of clinical and radiological presentation of childhood AIS, the studies undertaken in this thesis suggest that there is an unfavourable imbalance between endothelial injury and repair, and excess hypecoagulability in children with recurrent AIS. These novel observations provide unique insights into the pathophysiology of paediatric AIS