Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE Study

Studies have shown that albuminuria is associated with increased risk for cardiovascular events. We tested the relationship between albuminuria (UACR) and cardiovascular risk in 8206 hypertensive patients with left ventricular hypertrophy included in the LIFE Study. Follow-up was 39,122 patient years. The risk for the primary composite cardiovascular end point increases continuously from the lowest to the highest decile of baseline UACR. No specific threshold could be identified. In conclusion, albuminuria predicts the outcome in the LIFE Study. The risk for cardiovascular morbidity and mortality among hypertensive patients with left ventricular hypertrophy increases at much lower UACR than has been reported in diabetic patients.     

Physiologic-insensitive left ventricular assist predisposes right-sided circulatory failure: a pilot simulation and validation study

Right-sided circulatory failure (RSCF) is a serious complication in 15-30% of patients receiving a left ventricular assist device (LVAD). It is hypothesized that left ventricular support which lacks physiologic properties predisposes to RSCF. An integral computer simulation and experimental validation protocol was performed. The results suggest that with conventional insensitive left ventricular support right-sided circulatory function is compromised, which may form a substrate for the onset or progress of RSCF. Feedback control of the LVAD could provide a means to counter this problem. A control concept for the LVAD which aims to preserve right-sided circulatory function, while supporting peripheral perfusion, is proposed     

Peroxisomal biogenesis disorder: comparison of conventional MR imaging with diffusion-weighted and diffusion-tensor imaging findings

BACKGROUND AND PURPOSE: Peroxisomal biogenesis disorders (PBDs) refer to a group of disorders of peroxisomal biogenesis causing neuronal migration disorder, delayed myelination, and demyelination. The aim of this study was to evaluate the added value of diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) compared with that of conventional T2-weighted imaging in assessing the extent of white matter damage in patients with PBDs. METHODS: Three patients (aged 12, 16, and 80 months) with PBD (type 1 protein targeting sequence [PTS1]) and three age-matched control subjects underwent MR imaging on a 1.5-T system. The protocol included axial T2-weighted, DWI, and DTI sequences. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) changes were calculated using regions of interest at several predefined white matter areas and compared with those of age-matched control subjects. Color-coded maps were obtained to visualize the range of FA values. RESULTS: On the T2-weighted images, one patient revealed severe hypomyelination throughout the brain; the two other patients showed focal abnormal high-signal-intensity areas. All patients had significantly decreased FA values in white matter areas that appeared abnormal on the T2-weighted images. In two of the three patients, significant FA reduction was also found in normal-appearing white matter. The ADC values of the patients were significantly increased compared with those of the age-matched controls. CONCLUSION: Although based on a small number of patients, our data suggest that DWI and DTI can be used to characterize and quantify white matter tract injury in patients with PBD-PTS1. Furthermore, our data suggest that these techniques have the potential to identify neurodegenerative changes not yet visible on T2-weighted images.     

Organizing the transfer of patient care information: the development of a computerized resident sign-out system

BACKGROUND: The problem of safe and efficient transfer of care has increased over the years as new and complex diagnostic tools and more complex treatment options became available. Traditionally, residents ensured continuity of care by working long hours and minimizing the transfer of significant diagnostic or therapeutic responsibilities to other providers. The new 80-hour workweek has curtailed that practice and increased the pressure on trainees for workflow efficiency. We report on a study of information-handling routines among residents for the separate tasks of transfer of care ("sign-out") and daily patient care work (ward work). Using these results, an institution-wide computerized system was developed to centralize information-handling tasks and facilitate the management and transfer of patient care information. STUDY DESIGN: House staff from 31 resident-run inpatient and consult services at 2 teaching hospitals described current methods of maintaining patient information used during ward rounds and during sign-out. A subgroup of 28 residents then participated in the design of a computerized resident sign-out system to centralize patient information and produce lists for rounding and transferring care duties. Accuracy, flexibility, and portability were identified as key elements by the design team. RESULTS: Analysis of the type of information handled by residents caring for inpatients at our institution demonstrated common elements across many services. Most services used a paper patient list to manage both nightly sign-out and daily ward work, which required repeated recopying of patient data during the day. Utilizing medical information systems tools and rapid application development concepts, we constructed a computerized resident sign-out system ("UWCores"). This system combines the patient sign-out and daily ward work information in one central location. We believed this would improve the quality of information transferred during sign-out and enhance resident efficiency. During the design process, we identified rules that govern the type of clinical information that should be automatically versus manually updated. We observed an immediate acceptance by all residents and services that tried the system. CONCLUSIONS: This study shows that by combining downloaded patient data from hospital systems with resident-entered patient details, a computerized resident sign-out system can be a feasible, powerful, and popular tool. While its effect on patient safety and resident efficiency await the results of further studies, our study shows that this tool rapidly captured the attention of resident physicians and became widely used as a valuable means to centralize and organize sign-out and daily ward work information.     

The alpha2-5'AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading

The 5'AMP-activated protein kinase (AMPK) is a potential antidiabetic drug target. Here we show that the pharmacological activation of AMPK by 5-aminoimidazole-1-beta-4-carboxamide ribofuranoside (AICAR) leads to inactivation of glycogen synthase (GS) and phosphorylation of GS at Ser 7 (site 2). In muscle of mice with targeted deletion of the alpha2-AMPK gene, phosphorylation of GS site 2 was decreased under basal conditions and unchanged by AICAR treatment. In contrast, in alpha1-AMPK knockout mice, the response to AICAR was normal. Fuel surplus (glucose loading) decreased AMPK activation by AICAR, but the phosphorylation of the downstream targets acetyl-CoA carboxylase-beta and GS was normal. Fractionation studies suggest that this suppression of AMPK activation was not a direct consequence of AMPK association with membranes or glycogen, because AMPK was phosphorylated to a greater extent in response to AICAR in the membrane/glycogen fraction than in the cytosolic fraction. Thus, the downstream action of AMPK in response to AICAR was unaffected by glucose loading, whereas the action of the kinase upstream of AMPK, as judged by AMPK phosphorylation, was decreased. The fact that alpha2-AMPK is a GS kinase that inactivates GS while simultaneously activating glucose transport suggests that a balanced view on the suitability for AMPK as an antidiabetic drug target should be taken.     

Intestinal injury after thoracic aortic cross-clamping in the pig

BACKGROUND: The mucosal surface epithelium is an essential part of the functional intestinal barrier, but its structural response to ischemia/reperfusion is only partly characterized. The purpose of this study was to provide a detailed morphological evaluation of intestinal surface epithelium after aortic cross-clamping. MATERIAL AND METHODS: Pigs were subjected to thoracic aortic cross-clamping for 60 min and subsequent reperfusion for 120 min. Tissue blood flow and high-energy phosphates were measured with microspheres and HPLC, respectively. Urinary excretion of (14)C polyethylene glycol (MW 4000 Da) (PEG-4000), loaded into an intestinal loop, provided an index of intestinal permeability. RESULTS: Jejunal blood flow was restored at 10 min after aortic declamping. Denudation of the basement membrane of the intestinal villi tips, as a consequence of epithelial shedding, increased markedly during the initial 60 min of reperfusion (P = 0.002). During the following 45 min, the denuded basement membrane was partly covered with low cuboidal and squamous-shaped cells extending lamellipodia over a wavy basement membrane. Restoration of ATP at 60 min after aortic declamping correlated inversely to the extent of denuded basement membrane (r = 0.75, P = 0.032). Permeability of PEG-4000 increased markedly after aortic declamping and was linearly correlated to the area of denuded basement membrane (r = 0.87, P = 0.01). CONCLUSIONS: Reperfusion for 2 h after aortic cross-clamping is associated with initial aggravation of ischemia-induced injury in the porcine jejunum, but thereafter with restitution of the surface epithelium. Restoration of ATP may be important to avoid intestinal injury after ischemia. Increased permeability of a macromolecule in response to reperfusion is closely correlated to injury of the surface epithelium.