Traditional and emerging risk factors for cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of death in the United States and most western societies, further, approximately 50% of CVD is related to coronary heart disease (CHD). Most CVD results from an athero-thrombotic pathologic process in the body's arterial beds, and is largely preventable through risk factor reduction. Risk factors are diseases, physiologic states, biologic markers, or other identifiable factors associated with increased incidence of CVD. This article breaks down traditional, emerging,and possible risk factors for discussion.     

Serine 68 phosphorylation of phospholemman: acute isoform-specific activation of cardiac Na/K ATPase

OBJECTIVE: The mechanism by which the cardiac Na/K ATPase (NKA) is regulated by phosphorylation is controversial. We have used the perforated-patch technique to limit cell dialysis and maintain conditions as near physiological as possible. METHODS: NKA pump current (I(p)) was measured in isolated guinea pig ventricular myocytes, and its components (I(alpha 1) and I(alpha 2)) defined by their differing dihydroouabain sensitivities. RESULTS: Treatment with 1 micromol/l forskolin for 4 min at 35 degrees C caused a significant increase in I(alpha1) of 36+/-15% (P<0.05, n=6), but no change in I(alpha2). The presence of the PKA selective inhibitor H89 (50 micromol/l) throughout the protocol blocked the effect of the forskolin on I(alpha1). Treatment with H89 alone did not change I(alpha 1) or I(alpha 2). Isoelectric focusing gels of the NKA alpha1 subunit demonstrated six charge states, which were unaltered following treatment with forskolin. Western blots using an antibody specific for the PKA phosphorylation consensus site on the alpha1 subunit showed no change in the phosphorylation status of this residue following forskolin treatment. The sarcolemmal protein phospholemman (PLM) was found associated with NKA alpha 1 but not alpha 2 subunits by immunoprecipitation and immunofluorescence. PLM was phosphorylated at serine 68, but not 63, following treatment with forskolin. CONCLUSIONS: PKA-dependent, alpha 1-specific NKA activation may be mediated through phosphorylation of the accessory protein PLM, rather than direct alpha1 subunit phosphorylation.     

Bidirectional glenn shunt surgery using lepirudin anticoagulation in an infant with heparin-induced thrombocytopenia with thrombosis

There are few reports of the management of pediatric patients with heparin-induced thrombocytopenia (HIT) requiring cardiac surgery using currently available anticoagulants. We report a case of an infant with HIT requiring a bidirectional Glenn shunt who was successfully managed using lepirudin (r-hirudin, Refludan; Aventis, Bridgewater, NJ). Dosing and monitoring of anticoagulation were difficult, and we suggest caution in the use of lepirudin for cardiac surgery unless reliable monitoring of the degree of anticoagulation becomes available.     

Surgical biopsy in lymphoma

The term 'lymphoma' describes malignant lymphoproliferative diseases that originate from B- and T-cells in the lymphatic system. The majority of lymphomas arise from lymph nodes, while some may originate in extranodal sites. Lymphoma is a common cancer, affecting approximately 4000 people in Australia per year, and constituting 4% of newly diagnosed cancers. Lymphoma is primarily a disease of adults, and is the sixth most common cancer in men, after prostate, colorectal, lung, melanoma and bladder, and the fifth most common cancer in women, after breast, colorectal, melanoma and lung.     

Acute regulation of epithelial sodium channel by anionic phospholipids

Anionic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP(2)) and phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) are normally located in the inner leaflet of the plasma membrane, where these anionic phospholipids can regulate transmembrane proteins, including ion channels and transporters. Recent work has demonstrated that (1) ATP inhibits the renal epithelial sodium channel (ENaC) via a phospholipase C-dependent pathway that reduces PIP(2), (2) aldosterone stimulates ENaC via phosphoinositide 3-kinase, and (3) PIP(2) and PIP(3) regulate ENaC. Several lines of evidence show that ATP stimulation of purinergic P2Y receptors hydrolyzes PIP(2) and that aldosterone stimulation of steroid receptors induces PIP(3) formation. These studies together suggest that one primary mechanism for regulating ENaC is by alteration of anionic phospholipids and that the receptor-mediated and hormonal regulation of ENaC works through a variety of signaling pathways, but many of these pathways finally alter ENaC activity by regulating the formation or degradation of anionic phospholipids. Therefore, changes in the concentration of PIP(2) and PIP(3) are hypothesized to participate in the regulation of ENaC by purinergic and corticoid receptors. The underlying mechanism may be associated with a physical interaction of the positively charged cytoplasmic domains of the beta- and gamma-ENaC with the negatively charged membrane phospholipids. The exact nature of this interaction will require further investigation.     

Neonatal endotoxemia affects heart but not kidney bioenergetics

Purpose: The aim was to determine the effects of early and late endotoxemia on neonatal cardiac and renal mitochondrial energetics. Methods: Suckling rats received intraperitoneal 300 [mu ]g/kg lipopolysaccharide; controls received saline. Heart and kidney mitochondria were isolated after 2 hours (early) or 6 hours (late sepsis). State 3 (maximum mitochondrial flux) and 4 O₂ consumption and complex I activity were measured. Results, expressed as mean [plusmn] SEM normalized to citrate synthase (CS), were compared using paired t tests. Results: Mortality rate was zero within 2 hours, 2.7% between 2 and 6 hours of endotoxemia, and 100% 6 to 8 hours; therefore, we consider that 2 hours and 6 hours represent early and late endotoxemia, respectively. Endotoxic heart mitochondria had unaltered O₂ consumption at 2 hours but significantly decreased state 3 after 6 hours, resulting in significantly decreased respiratory control ratio. Complex I activity, which could affect O₂ consumption, was decreased significantly at 6 hours (9.8 [plusmn] 0.6 mU/U CS; n [equals] 15) versus controls (11.3 [plusmn] 0.8, n [equals] 15; P [equals] .04), but not at 2 hours. There were no differences in these measurements at either 2 hours or 6 hours in kidney mitochondria. Conclusions: The respiratory chain is affected late in endotoxemia. Neither early nor late endotoxemia affects oxidative function of kidney mitochondria. J Pediatr Surg 38:690-693. [copy ] 2003 Elsevier Inc. All rights reserved.     

Relative performance of the level 1 and ranger pressure infusion devices

Pressure infusion devices are often used to administer fluids in the operating room, but they may rarely be associated with serious venous air embolism. We studied the performance of the Level 1 and the Ranger Pressure Infusor in the laboratory. The Ranger delivered less air and delivered fluid faster than the Level 1 but did not warm fluid or blood as well. Although the Ranger device may be safer in terms of the risk of air embolism, its inferior warming performance shows that the optimal pressure infusion device has yet to be manufactured. IMPLICATIONS: Pressure infusion devices are widely used to treat patients with large-volume blood loss. The use of these devices may subject patients to the risk of venous air embolism. Our study found the new Ranger device to be superior to the widely used Level 1 in air elimination.     

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.