Asymptomatic isolated microscopic haematuria: long-term follow-up

BACKGROUND: Evidence to support current diagnostic and management approaches to asymptomatic haematuria is lacking and based on short-term clinical observation. AIM: To ascertain the natural history and long-term outcome of asymptomatic and isolated haematuria, and to determine the clinical correlates of adverse renal events. DESIGN: Prospective observational referral-based study. METHODS: We evaluated 90 consecutive patients with isolated microscopic haematuria, first seen between 1985 and 1996 at an out-patient nephrology clinic. We defined adverse renal events as the development of proteinuria (> 0.5 g/24 h) on two consecutive occasions, development of hypertension, or impaired renal function characterized by glomerular filtration rate (GFR) of <60 ml/min/1.73 m(2) for 3 months or more. RESULTS: There were 24 males and 66 females, median follow-up 5.2 years (total 442 patient-years). Mean age at presentation was 39 +/- 13 years. Fifteen (17%) had complete resolution of microscopic haematuria. One (1%) had transitional cell carcinoma of urinary bladder 20 months after initial presentation. Twelve (13%) developed hypertension, and 10 (11%) proteinuria. Only one developed chronic renal failure, 2.3 years after initial presentation. Altogether, 16 (19%) developed at least one adverse event, after a mean 42 months. Neither history of renal biopsy nor histological diagnosis of glomerular disease was predictive of renal events. Three independent variables were predictive of adverse renal events: baseline proteinuria (RR per 0.1 g/day 2.04; 95%CI 1.13-3.68; p = 0.018); MDRD-estimated GFR at presentation (RR per 10 ml/min/1.73 m(2) decrement 2.01; 95%CI 1.09-3.71; p = 0.025); and baseline serum urate (RR per 100 micromol/l 1.02; 95%CI 1.01-1.03; p = 0.009). DISCUSSION: Asymptomatic microscopic haematuria can lead to adverse renal events, and warrants nephrologist evaluation and regular follow-up. Its isolated microscopic haematuria is closely related to early hints of chronic kidney disease, such as low-grade proteinuria and renal insufficiency, as well as hyperuricaemia.     

Role for myosin II in regulating positioning of Salmonella-containing vacuoles and intracellular replication

Salmonella enterica serovar Typhimurium grows within host cells in a permissive compartment termed the Salmonella-containing vacuole (SCV). These bacteria use two distinct type III secretion systems (T3SS) to deliver virulence proteins (effectors) into cells. Effectors secreted by the Salmonella pathogenicity island 1 (SPI-1)-encoded T3SS mediate invasion and early SCV maturation steps, while those secreted by the SPI-2 T3SS affect the SCV at later stages postinfection. Some SPI-2 effectors modulate microtubule motor activity on the SCV. Here, we show that the actin-based motor myosin II also affects SCV dynamics during infection. Following invasion, myosin II is required for SCV positioning near the nucleus of host cells. Later, myosin II counteracts the activities of the SPI-2 effectors PipB2 and SseJ to maintain SCV positioning and stability, respectively. Myosin II activity was required for maximal bacterial growth in macrophages. Rho kinase activity was required for SCV positioning. The effector SopB, a known activator of Rho GTPases, was found to be required for SCV positioning, and transfection of cells with SopB was sufficient to induce myosin II phosphorylation. These studies reveal a novel role for myosin II in controlling SCV dynamics during infection and suggest that SopB activates myosin II.     

罗陆一教授望诊辨治冠心病经验

广东省名中医罗陆一教授、主任医师行医四十余载,临床经验丰富,对心血管疾病的诊断治疗有独到之处,介绍其在临床上望诊辨治冠心病之经验。     

A multiplex qPCR assay for transgenes detection: A novel approach for gene doping control in horseracing using conventional laboratory setup

Illicit administration of transgene into horses is a form of gene doping that has been a key concern in equine sports. The large number of potential performance-enhancing transgenes has demanded a cost-effective and reliable detection method. Multiplex qPCR is a relevant technique, but the cross-talking between fluorophores and high background noise limits the method sensitivity and specificity. This study reports a simpler multiplexing approach by using the same fluorophore for four hydrolysis probes each targeting one of the four transgenes: human growth hormone, insulin-like growth factor 1, equine erythropoietin and interleukin-10. Any positive findings from this multiplex qPCR assay can then be confirmed by individual qPCR assays to identify potential transgene(s). This has effectively eliminated the cross-talking issue and allowed an improved signal-to-noise than conventional multiplex qPCR assay. It has also removed the limitation imposed by the available choice of fluorophores and optical channels of qPCR instruments on the number of transgenes that can be analysed in a multiplex qPCR assay. This novel multiplex qPCR has been successfully validated. The estimated limits of detection were ~1500–2500 copies/mL of blood, thus demonstrating comparable sensitivity with the corresponding duplex qPCR assays. Concurring results were obtained by analysing hundreds of official blood samples provided by racehorses with this multiplex qPCR assay and the accredited individual duplex qPCR assays. This novel multiplex qPCR assay for detecting multiple transgenes is a cost-effective screening method using a conventional laboratory setup and has opened up the potential to include the testing of additional transgenes in a single assay.     

From MIA to FIFA: The vicious matrix of frailty,inflammation, fluid overload and atherosclerosis in peritoneal dialysis

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Two decades ago, the common co-existence of malnutrition and systemic inflammation PD patients with atherosclerosis and CVD led to the proposed terminology of ‘malnutrition-inflammation-atherosclerosis (MIA) syndrome’. Although the importance of malnutrition is well accepted, frailty represents a more comprehensive assessment of the physical and functional capability of the patient and encompasses the contributions of sarcopenia (a key component of malnutrition), obesity, cardiopulmonary as well as neuropsychiatric impairment. In recent years, it is also increasingly recognized that fluid overload is not only the consequence but also play an important role in the pathogenesis of CVD. Moreover, fluid overload is closely linked with the systemic inflammatory status, presumably by gut oedema, gastrointestinal epithelial barrier dysfunction and leakage of bacterial fragments to the systemic circulation. There are now a wealth of published evidence to show intricate relations between frailty, inflammation, fluid overload and atherosclerotic disease in patients with chronic kidney disease (CKD) and those on PD, a phenomenon that we propose the term ‘FIFA complex’. In this system, frailty and atherosclerotic disease may be regarded as two patient-oriented outcomes, while inflammation and fluid overload are two inter-connected pathogenic processes. However, there remain limited data on how the treatment of one component affect the others. It is also important to define how treatment of fluid overload affect the systemic inflammatory status and to develop effective anti-inflammatory strategies that could alleviate atherosclerotic disease and frailty.