C-reactive protein: a marker or a player?

It has been suggested that Type 2 diabetes may, in part, be precipitated or accelerated by an acute-phase reaction as part of the innate immune response, in which large amounts of cytokines are released from adipose tissue, creating a low-grade inflammatory milieu. There is also firm evidence that atherosclerosis is an immune-mediated inflammatory disease. Therefore it is reasonable to imply that low-grade inflammation is an important pathogenetic factor in atherosclerosis and cardiovascular events in patients with Type 2 diabetes. Over the last few years, there have been a lot of promising clinical markers proposed to link inflammation and atherosclerosis. Of these markers, hs-CRP (high-sensitivity C-reactive protein) might be a prognostic marker for further cardiovascular events, although this has been refuted recently. In this issue of Clinical Science, Castoldi and co-workers have demonstrated that, in patients with Type 2 diabetes categorized into low (<1.0 mg/l), medium (1.0-3.0 mg/l) and high (>3.0 mg/l) hs-CRP groups, serum levels of hs-CRP correlated with lipopolysaccharide-stimulated release of interleukin-1beta and interleukin-6 in whole blood. This finding may indicate that low-grade inflammatory activity might influence cytokine production in these patients.     

Plasma disappearance of indocyanine green: a marker for excretory liver function?

Objective To investigate whether the plasma disappearance rate of indocyanine green (ICG) assessed using a commercially available bedside monitor provides an accurate estimation of cumulative biliary ICG excretion in a clinically relevant model of long-term, hyperdynamic porcine endotoxemia.Design and setting Prospective experimental study in the animal laboratory in a university hospital.Subjects Fifteen domestic pigs.Interventions Pigs were anesthetized, mechanically ventilated, and instrumented. Intravenous endotoxin was continuously infused over 12 h concomitant with fluid resuscitation. Measurements were performed before and 12 h after the start of endotoxin infusion.Measurements and results All animals developed hyperdynamic circulation characterized by a sustained increase in cardiac output. Despite well maintained portal venous and consequently total liver blood flow endotoxemia decreased hepatic lactate uptake, which was accompanied by a significant fall in portal and hepatic venous pH. Both the cumulative bile flow and biliary ICG and bicarbonate excretion measured during 1 h after intravenous bolus of 25 mg ICG fell significantly. By contrast, neither the plasma disappearance rate of ICG nor the rate corrected for liver blood flow exhibited any changes over time.Conclusions In hyperdynamic porcine endotoxemia the plasma disappearance rate of ICG failed to accurately substitute for direct short-term measures of biliary ICG excretion. Hence normal values of plasma disappearance rate of ICG should be interpreted with caution in early, acute inflammatory conditions.A. Stehr and F. Ploner contributed equally to this studyThis research was supported by Deutsche Forschungsgemeinschaft (Ra 396/3-1) and a research fellowship from the Alexander von Humboldt Stiftung (M.M.)     

Indexing of renal function parameters by body surface area: intelligence or folly?

Indexation of glomerular filtration rate (GFR) by body surface area (BSA) is often done without raising any questions. In this article, we will shortly review the limitations of such indexation and illustrate potential errors in clinical practice due to this indexation. Adjusting the GFR by BSA is particularly misleading in patients with abnormal body size (obese and anorectic). We will also insist on the fact that indexation by BSA is not required for the GFR longitudinal follow-up. Additionally, we will discuss the implications and consequences of BSA indexation on the creatinine-based equations, such as the Cockcroft-Gault and the MDRD study equations.     

Just heavy menses or something more? Raising awareness of von Willebrand disease

OVERVIEW: Von Willebrand disease is the most common inherited bleeding disorder, with an estimated prevalence of up to 1.3% of the U.S. population, or 4 million Americans. It's caused by a deficiency of or defects in von Willebrand factor, a protein necessary for blood to clot. Many nurses and other health care providers, as well as patients, are unaware of the disorder, its symptoms, and its associated risks. Although the disorder occurs equally in males and females, it can be more troublesome in females. Heavy menses beginning at menarche is one of the most common presentations, but because the disorder is inherited and other family members may have similarly heavy menses, the assumption may be that this is normal. This article describes von Willebrand disease and its three types, explains how to recognize and investigate suggestive symptoms, and outlines management strategies.     

Cystatin C: an improved estimator of glomerular filtration rate?

BACKGROUND: Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR. APPROACH: In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using "cystatin c" as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted "gold standards" for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations. CONTENT: This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients. SUMMARY: Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations.     

Sialic acid: a novel marker of cardiovascular disease?

The global burden posed by cardiovascular disease (CVD), due to a rising incidence of known risk factors, underlines an urgent need to identify other potential risk factors. Sialic acid (SA), an abundant terminal monosaccharide of glycoconjugates, is a possible risk factor for CVD. Although large-scale epidemiological surveys have shown that serum total sialic acid (TSA) is positively associated with mortality from coronary artery disease (CAD) and stroke, studies investigating the correlation between serum TSA and the severity of atherosclerosis are conflicting. Clinical and epidemiological studies indicate that serum TSA is a marker of a sustained inflammatory response in CVD, rather than causal in nature. Data also indicates ethnic variation in baseline TSA. This article reviews current methods for determining serum TSA and evidence supporting serum TSA as a risk factor for CVD. Potential mechanisms for this role are examined. The use of serum TSA as a marker of atherosclerotic disease is evaluated.