Joseph H. Keffer

Effects of repeated electrical defibrillations on cardiac troponin I levels

Multiple endocardial countershocks applied during intraoperative endocardial implantable cardioverter-defibrillator testing for the purpose of defibrillation threshold determination resulted in detectable myocardial injury in 5 of 12 patients, as indicated by elevations in cardiac troponin I levels. This injury was not associated with acute changes on the surface electrocardiogram.

Discriminating Between Iron Deficiency Anemia and Anemia of Chronic Disease Using Traditional Indices of Iron Status vs Transferrin Receptor Concentration

We compared the ability of soluble serum transferrin receptor (TfR) concentration, quantified using the R&D Systems (Minneapolis, MN) enzyme-linked immunosorbent TfR assay, with other, more traditional indicators of iron status (total iron binding capacity [TIBC], mean corpuscular volume [MCV], percent transferrin saturation [%TS], RBC distribution width [RDW], and serum iron concentration [SIC]) for discriminating between patients with iron deficiency anemia (IDA) or anemia of chronic disease (ACD). The TfR concentration was determined in 72 serum samples selected from men and nonpregnant women classified biochemically on the basis of ferritin concentration as having IDA (n = 41) or ACD (n = 31). By using receiver operating characteristic curve analysis, the diagnostic accuracy of the various indicators of iron status that we evaluated for discriminating between IDA and ACD decreased in the following order: TIBC > TfR > MCV > (%TS = RDW) > SIC. There was no significant difference between the diagnostic accuracy of TIBC and TfR. Thus, the routine measurement of TfR offers no advantage over TIBC for discriminating between people with biochemically defined IDA or ACD.

Maternal cardiac troponin I levels during normal labor and delivery

OBJECTIVEnDiagnosis of myocardial infarction in pregnant women on the basis of changes in biochemical markers is complicated by the release of some of these markers from noncardiac tissue sources. We compared troponin I levels with those of other markers in normal pregnant women.nnnSTUDY DESIGNnIn 51 healthy women at term in labor, cardiac troponin I, myoglobin, creatine kinase, and creatine kinase MB levels were determined at admission, during the second stage of labor, and within 30 minutes, 12 hours, and 24 hours after delivery.nnnRESULTSnMean admission levels for all markers were below the upper limit of normal. Mean concentrations of myoglobin, creatine kinase, and creatine kinase MB mass were increased nearly twofold within 30 minutes after delivery. The highest level of troponin I (0.134 ng/mL) at all time points was below the cutoff value (0.15 ng/mL) for discriminating myocardial infarction.nnnCONCLUSIONSnBecause only troponin I levels remained undetectable during and after delivery, it is potentially the most useful biochemical marker for monitoring pregnant women for myocardial injury.

Effects of Cocaine on Cortisol Secretion in Humans

The effects of acute cocaine administration on the pituitary adrenal axis in humans without a history of drug abuse are unknown. The authors studied 12 male volunteers twice in a double-blinded, placebo-controlled, randomized fashion. After intranasal administration of 2 mg/kg cocaine, cortisol levels were significantly higher than after placebo administration. The authors concluded that acute administration of cocaine to humans increases cortisol secretion.

Soluble transferrin receptor (sTfR) concentration quantified using two sTfR kits: analytical and clinical performance characteristics

We compared the analytical and clinical performance characteristics of the Ramco and R&D Systems enzyme-linked immunosorbent assays (ELISAs) for quantifying serum levels of soluble transferrin receptor (sTfR). In addition, we determined both the number of samples required to determine the true individual mean sTfR concentration for a single individual and the critical difference (CD) between serial measurements that indicates a statistically significant change in sTfR concentration. sTfR concentration was determined in 127 serum samples selected retrospectively from males (n=32) and non-pregnant (n=40) and pregnant women (n=55). Intra- and inter-assay precision for both methods was good (CV values 5--10%) to excellent (CV values <5%) over a wide range of sTfR concentrations. Correlation between these methods was good (r=0.93); however, sTfR values by the R&D kit were approximately 2.9 times higher than values obtained using the Ramco kit on the same serum samples. Nevertheless, receiver-operator characteristic (ROC) curve analysis demonstrated that the diagnostic accuracy of both assays in discriminating between patients with iron-deficiency anemia (IDA) or anemia of chronic disease (ACD) was high (area-under-the-curve (AUC) values >0.95) and not significantly different (P=0.480). We determined that a minimum of 8 samples are required to determine an individuals true sTfR concentration, while a >40% difference between serial sTfR measurements would be required to indicate a statistically significant change in sTfR concentration. We concluded that both the Ramco and R&D Systems sTfR methods have similar analytical and clinical performance characteristics and were likely to be equally useful in discriminating between patients with biochemically defined IDA or ACD.

False-positive serum prostate-specific antigen values in a patient with non-hodgkin lymphoma of the kidney

Prostate-specific antigen (PSA) is the clinically most useful tumor marker for prostate cancer. Although false-positive elevations have been reported due to disease processes outside the prostate gland with the use of the polyclonal assay, such false-positive test results have been exceedingly rare with the use of the monoclonal assay. We report the case of a patient diagnosed with a B-cell lymphoma of the kidney and a significant elevation of serum PSA levels by monoclonal assay in the absence of either inflammatory or malignant prostate disease. PSA returned to normal during lymphoma-specific chemotherapy with a cyclophosphamide, mechlorethamine, vincristine, procarbazine, prednisone regimen. Possible explanations and clinical implications are discussed.

ENDOCRINOPATHY AND ECTOPIC HORMONES IN MALIGNANCY

This article reports progress in the field of endocrinopathies and focuses on the molecular aspects of these diseases. Implications for genetics and metabolic study are presented. Although limitations of earlier approaches are confirmed, progress is noted, particularly with regard to the contribution of octreotide scintigraphy. Integrated with the evolving applications of molecular insights, significant clinical progress has been recorded.

Can sepsis be better defined? Contribution of a novel assay for endotoxin

Abstract Sepsis is the leading killer of ICU patients and the 11th leading cause of death overall. One of the greatest challenges in sepsis is rapidly and accurately identifying patients who have it. Establishing an infectious component of sepsis rather than a non-infective cause of the systemic inflammatory response syndrome can be extremely difficult. Endotoxin is a known potent trigger of the sepsis cascade. Using the Endotoxin Activity Assay (Spectral Diagnostics, Toronto, Ontario, Canada) for endotoxin measurement, we report findings from an observational clinical trial exploring endotoxin levels, infection status, and sepsis in ICU patients. Microbiologically proven infection was relatively uncommon in this group of patients, as in other series, despite the fact that many met criteria for sepsis. Moreover, the results are available long after physicians need the information. As such, the inclusion of infection in the definition of sepsis should be revisited. Endotoxemia may be a more clinically relevant marker of sepsis.