Massive right atrial myxoma

Right atrial myxomas are uncommon and are often detected incidentally in asymptomatic individuals. We describe a case of a massive right atrial myxoma that was suspected following an abnormal right heart border on a chest X-ray and an abnormal 12 lead electrocardiogram.     

Prosthetic mitral valve thrombosis,malfunction, and paroxysmal mitral regurgitation

Intermittent dysfunction of mechanical mitral valve prosthesis is an uncommon condition. It carries serious clinical implications if unrecognized. Here, we present a case of a 28‐year‐old female with a history of rheumatic multivalvular disease, for which she had undergone double valve replacement and tricuspid annuloplasty. Six months later, she presented with heart failure. Clinical examination revealed intermittent loss of closing clicks followed by a pansystolic murmur at the apex, suggestive of mitral prosthetic valve dysfunction. We highlight the echocardiographic findings of paroxysmal mitral valvular regurgitation secondary to prosthetic valve malfunction secondary to prosthetic valve thrombosis.     

Quantitation and localization of blood-to-brain influx by magnetic resonance imaging and quantitative autoradiography in a model of transient focal ischemia.

The ability of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced MRI to localize and quantitate blood-brain barrier (BBB) opening was evaluated against quantitative autoradiographic (QAR) imaging of (14)C-alpha-aminoisobutyric acid (AIB) distribution. The blood-to-brain transfer constant (K(i)) for Gd-DTPA was determined by MRI in rats after 3 h of focal cerebral ischemia plus 2.5 h of reperfusion (n = 9), and that of AIB was determined by QAR shortly thereafter. Tissue regions of interest (ROIs) for Gd-DTPA leakage were identified by ISODATA segmentation of pre- and post-Gd-DTPA Look-Locker (L-L) T(1) maps. Patlak plots were constructed using time course of blood and tissue T(1) changes induced by Gd for estimating K(i). Among the nine rats, 14 sizable regions of AIB uptake were found; 13 were also identified by ISODATA segmentation. Although the 13 MRI-ROIs spatially approximated those of AIB uptake, the segmentation sometimes missed small areas of lesser AIB uptake that did not extend through more than 60% of the 2.0-mm-thick slice. Mean K(i)'s of AIB were highly correlated with those of Gd-DTPA across the 13 regions; the group means (+/-SD) were similar for the two tracers (7.1 +/- 3.3 x 10(-3) and 6.8 +/- 3.5 x 10(-3) ml.g(-1) . min(-1), respectively). In most instances, Gd-DTPA MRI accurately localized areas of BBB opening.     

Optimizing measurement of self-reported adherence with the ACTG Adherence Questionnaire: a cross-protocol analysis

BACKGROUND/OBJECTIVE: The AIDS Clinical Trials Group (ACTG) Adherence Questionnaire is used extensively, but investigators frequently only use the first item of the questionnaire (4-day recall). DESIGN/METHODS: A secondary analysis was conducted to (1) estimate the validity and reliability of each of the 5 scale items and (2) compare the approach commonly used to summarize adherence data collected with the instrument (average 4-day recall) with alternate approaches derived using principal component (PC) analysis and the full questionnaire. We hypothesized that an estimate of adherence taking all items of the questionnaire into account would provide a stronger measure of adherence. RESULTS: Logistic regression analyses showed that the first PC identified (PC1) was significantly correlated with plasma HIV RNA outcome (P < 0.0001 for ACTG 370 data and P = 0.006 for ACTG 398 data) and correlated with plasma HIV RNA better than average 4-day recall. An adherence index formulated using weights of PC1 showed substantially greater variability in the range of adherence scores in comparison to average 4-day adherence recall alone. PC1 compared favorably with 2 indices derived from medication event monitoring system data as well. CONCLUSIONS: Findings indicate that a superior assessment of antiretroviral adherence may be obtained with the ACTG Adherence Questionnaire by using the method employed in this analysis.     

Preventing alcohol-exposed pregnancies: a randomized controlled trial

BACKGROUND: Prenatal alcohol exposure is a leading preventable cause of birth defects and developmental disabilities in the United States. DESIGN: A randomized controlled trial (2002-2005; data analyzed 2005-2006) of a brief motivational intervention to reduce the risk of an alcohol-exposed pregnancy (AEP) in preconceptional women by focusing on both risk drinking and ineffective contraception use. SETTING/PARTICIPANTS: A total of 830 nonpregnant women, aged 18-44 years, and currently at risk for an AEP were recruited in six diverse settings in Florida, Texas, and Virginia. Combined settings had higher proportions of women at risk for AEP (12.5% overall) than in the general population (2%). INTERVENTIONS: Participants were randomized to receive information plus a brief motivational intervention (n=416) or to receive information only (n=414). The brief motivational intervention consisted of four counseling sessions and one contraception consultation and services visit. MAIN OUTCOME MEASURES: Women consuming more than five drinks on any day or more than eight drinks per week on average, were considered risk drinkers; women who had intercourse without effective contraception were considered at risk of pregnancy. Reversing either or both risk conditions resulted in reduced risk of an AEP. RESULTS: Across the follow-up period, the odds ratios (ORs) of being at reduced risk for AEP were twofold greater in the intervention group: 3 months, 2.31 (95% confidence interval [CI]=1.69-3.20); 6 months, 2.15 (CI=1.52-3.06); 9 months, 2.11 (CI=1.47-3.03). Between-groups differences by time phase were 18.0%, 17.0%, and 14. 8%, respectively. CONCLUSIONS: A brief motivational intervention can reduce the risk of an AEP.     

Evaluation of a multiplex real-time polymerase chain reaction for the quantification of Escherichia coli O157 in cattle feces

Cattle are asymptomatic reservoirs for Escherichia coli O157, a major foodborne pathogen. The organism generally colonizes the hindgut of cattle and is shed in the feces at low concentrations. The objective of this research was to evaluate a multiplex, real-time polymerase chain reaction (mqPCR) assay for quantification of E. coli O157 in cattle feces using stx1, stx2, and rfbE gene targets. Primer efficiency and analytical sensitivity of the assay were evaluated with a single or pooled (five strain) culture of E. coli O157. In pure culture, the minimum detection limit of the assay was 1.4×10(3) CFU/mL and 3.6×10(3) CFU/mL for the single and five-strain mixture of E. coli O157, respectively. Diagnostic sensitivity was analyzed using DNA extracted from cattle feces spiked with E. coli O157. In feces spiked with the pooled mixture of five E. coli O157 strains, the minimum detection limit was 3.6×10(4) CFU/g. We also evaluated the assay with feces from cattle experimentally inoculated with E. coli O157 by comparing the results to a culture-based method. For the majority of samples tested, the concentration of E. coli O157 detected by the real-time and culture methods was within one log difference. However, the assay could only be evaluated for cattle shedding high concentrations of E. coli O157. In conclusion, the mqPCR quantifying E. coli O157 in cattle feces using stx1, stx2, and rfbE gene targets may have use in detecting and quantifying super shedders, but is not applicable for quantification in animals shedding low concentrations (10(2) to 10(3) CFU/g feces).     

Relationship between Albuminuria and Total Proteinuria in Systemic Lupus Erythematosus Nephritis: Diagnostic and Therapeutic Implications

Background and objectives: Albuminuria is regarded a sensitive measure of progression of glomerular disease. This study was undertaken in patients who had systemic lupus erythematosus glomerulonephritis (n = 57) and were followed in the Ohio SLE Study to determine whether measuring albuminuria offered clinical advantages over that of total proteinuria.Design, setting, participants, & measurements: Twenty-four-hour urine collections (n = 127) were obtained at baseline and annually for measurement of microalbumin, total protein, and creatinine.Results: There was a strong linear relationship between microalbumin-creatinine and protein-creatinine ratios over the entire range of protein-creatinine ratios; however, in the protein-creatinine ratio range 0.0 to 0.3, as the protein-creatinine ratio increased, the microalbumin-protein ratio increased much more than the protein-creatinine ratio. Also, the greater the protein-creatinine ratio, the greater was the evidence for nonselective proteinuria (protein-creatinine ratio − microalbumin-creatinine ratio).Conclusions: For the diagnosis of proteinuria renal flare, measuring albuminuria offers no advantage over measuring total proteinuria because changes in protein-creatinine and microalbumin-creatinine ratios are highly correlated over the designated ranges for systemic lupus erythematosus glomerulonephritis proteinuric flares. In those with normal-range proteinuria, subsequent changes in microalbumin-protein ratio might be a better forecaster of renal flare than changes in protein-creatinine or microalbumin-creatinine ratio. High protein-creatinine ratios are associated with evidence of nonselective proteinuria, which may increase the nephrotoxicity of proteinuria. Thus, using high-threshold criteria for systemic lupus erythematosus flare (allowing greater proteinuria increase before flare is declared) may expose the kidney to greater nephrotoxicity than using the low-threshold criteria for systemic lupus erythematosus flare.Glomerular injury usually induces an increase in glomerular permeability to macromolecules, resulting in increased urinary excretion of plasma proteins. Under conditions of severe glomerular injury, albumin (molecular weight approximately 69 kD) is the most abundant protein excreted in the urine, generally accounting for much more than 50% of the urinary proteins (1). Thus, albuminuria is the hallmark of glomerular proteinuria; however, under conditions of mild glomerular injury, albumin usually comprises much less than 50% of urinary proteins (1). The low rate of albuminuria compared with that of total proteinuria (albumin + nonalbumin proteinuria) in mild glomerular injury is thought to be the result, at least in part, of the greater capacity of the renal tubules to absorb filtered albumin compared with that of larger proteins such as IgG (molecular weight approximately 150 kD) (2–4). Hereafter, “total proteinuria” is referred to as proteinuria.The prime example of using albuminuria to monitor progression of early glomerular injury is in diabetic glomerulosclerosis, where increases in albuminuria are indicative of progression of diabetic glomerulosclerosis, even when the proteinuria rate is within the normal range (e.g., <200 mg/24 h) (5–8). For measurement of low-level changes in albuminuria, immunoassays have been developed to detect urine albumin in concentrations <1 mg/dl. These are referred to as “microalbumin” assays (1). Normal 24-h urine albumin excretion by these assays is <30 mg albumin/g creatinine (8). Albuminuria rates of 30 to 300 mg/g creatinine are referred to as “microalbuminuria.” Albuminuria rates beyond that range are referred to as “macroalbuminuria” (8). When the macroalbuminuria range is reached in diabetic nephropathy, albumin becomes the dominant urinary protein and proteinuria parallels albuminuria. At that point, the advantage of measuring albuminuria over proteinuria is generally lost (7).It is well established that in chronic kidney disease (CKD), albuminuria and proteinuria are highly correlated (7–9), particularly when 24-h proteinuria exceeds 500 mg (7); however, in systemic lupus erythematosus glomerulonephritis (SLE GN), the relationship between proteinuria and albuminuria has not been rigorously examined (10–12). It is plausible that albuminuria–proteinuria relationships are different in SLE GN compared with that of other forms of CKD. Mechanisms that could account for such differences include the following: (1) The microalbuminuria assay does not detect intact albumin that has been modified in vivo. The latter process is particularly common in patients with diabetes and CKD (13). The extent to which albumin is modified in SLE is unknown. (2) Albumin that undergoes glomerular filtration in CKD is extensively absorbed by the renal tubules. The fraction of albumin that is not absorbed undergoes extensive degradation, apparently by proximal tubular lysosomes, with excretion in urine as low molecular weight peptides <10 kD. These peptides are not measured by the immunoassay for microalbuminuria or by the usual clinical measures of proteinuria such as pyrogallol red or Coomassie blue (4,13,14). In experimental models of GN, renal tubular degradation of albumin does not occur (13,14). Thus, intact albumin could be overrepresented in SLE GN urine compared with that of CKD urine. (3) There is evidence from experimental models that some conditions of moderate albuminuria may be entirely the result of failure of renal tubular retrieval of albumin that normally is filtered by the normal glomerulus (15,16). Renal tubular albumin retrieval could differ between SLE and other CKD conditions. (4) Hypoalbuminuria independent of urine protein loss commonly occurs in SLE. The apparent mechanism is inflammation-induced albumin catabolism (17). This mechanism could influence albuminuria–proteinuria relationship in SLE GN compared with that of other causes of CKD in which inflammation is not a prominent feature. This study explores the relationship between albuminuria and proteinuria in patients with SLE GN across a wide range of proteinuria, including threshold ranges that commonly are used for identifying SLE proteinuric flares.     

A composite urine biomarker reflects interstitial inflammation in lupus nephritis kidney biopsies

The initial treatment of lupus nephritis is usually based on a renal biopsy. Subsequent disease flares, however, are often treated without the benefit of kidney pathology because repeat biopsies are infrequent. A noninvasive, real-time method to assess renal pathology would be useful to adjust treatment and improve outcome. To develop such a method we collected urine samples at or close to the time of 64 biopsies from 61 patients with lupus nephritis to identify potential biomarkers of tubulointerstitial inflammation and correlated these to biopsy parameters scored by a renal pathologist using a semiquantitative scale. Linear discriminant analysis was used to weight variables and derive composite biomarkers that identified the level of tubulointerstitial inflammation based on urine concentrations of monocyte chemotactic protein-1, hepcidin (a marker of active lupus), and liver fatty acid-binding protein. The discriminant function that described the most accurate composite biomarkers included urine monocyte chemotactic protein-1 and serum creatinine as the independent variables. This composite had sensitivity, specificity, positive predictive value, and negative predictive value of 100, 81, 67, and 100%, respectively. Only 14% of the biopsies were misclassified. Thus, specific renal pathologic lesions can be modeled by composite biomarkers to noninvasively follow and adjust the treatment of lupus nephritis reflecting renal injury.