Neonatal refractory supraventricular tachycardia: successful treatment with amiodarone

A 3-week-old neonate with supraventricular tachycardia unresponsive to traditional therapy was treated successfully with amiodarone. An electrophysiologic study suggested the presence of a concealed left-sided accessory atrioventricular pathway. Because of its significant side effects, amiodarone should be used only as a last resort in the treatment of neonatal supraventricular tachycardia.     

Transport of dibasic amino acids, cystine, and tryptophan by cultured human fibroblasts: absence of a defect in cystinuria and Hartnup disease

Transport of lysine, arginine, cystine, and tryptophan was studied in cultured skin fibroblasts from normal controls and from patients with cystinuria and Hartnup disease. Each of these amino acids was accumulated against concentration gradients by energy-dependent, saturable mechanisms. Lysine and arginine were each transported by two distinct processes which they shared with each other and with ornithine. In contrast, cystine was taken up by a different transport system with no demonstrable affinity for the dibasic amino acids. The time course and Michaelis-Menten kinetics of lysine and cystine uptake by cells from three cystinuric patients differed in no way from those found in control cells. Similarly, the characteristics of tryptophan uptake by cells from a child with Hartnup disease were identical to those noted in control cells. These findings indicate that the specific transport defects observed in gut and kidney in cystinuria and Hartnup disease are not expressed in cultured human fibroblasts, thus providing additional evidence of the important role that cellular differentiation plays in the regulation of expression of the human genome.     

Day‐to‐day variation in oxygen consumption at submaximal loads during ergometer cycling by adolescents

The day‐to‐day variation in oxygen consumption (V˙O₂) during ergometer cycling by 20 healthy adolescents, 10 females and 10 males, was measured using indirect calorimetry. The two sets of measurements were performed on two consecutive days. Great care was taken to minimize possible disturbing factors. Cycling started at 50 and 100 W for female and male adolescents, respectively. The load was increased at a rate of 5 W 30 s^?1. In order to reach steady state, the load was kept constant for 3·5 min twice during the cycling session, at 100 and 130 W for the females and at 130 and 160 W for the males. Cycling continued until exhaustion. The maximal loads were 196 W (mean) and 271 W (mean) for females and males, respectively. At the maximal loads the day‐to‐day variation (±2 SD) in oxygen consumption (V˙O₂) was ±330 ml min^?1 for females and 390 ml min^?1 for males. At the submaximal loads the day‐to‐day variation in heart rate (HR) was 9·3 beats min^?1 (±2 SD) (coefficient of variation, CV=3·4% at 130 W) for both sexes. The day‐to‐day variation in oxygen consumption (V˙O₂) was ±199 ml min^?1 (±2 SD) at the different submaximal loads and did not differ between female and male adolescents (CV=5·7% at 130 W). This natural day‐to‐day variation must be taken into consideration when using a submaximal ergometer cycling test for the evaluation of physical capacity in the two sexes.     

Effect of Heparin and Heparin Fractions on Platelet Aggregation

Porcine intestinal mucosal heparin induced aggregation of platelets in citrated platelet-rich plasma and enhanced platelet aggregation and serotonin secretion induced by other agents. This action of heparin was blocked by substances that elevate platelet cyclic AMP and by EDTA but not by inhibitors of platelet cyclooxygenase. The effect was not inhibited by apyrase or by N-amylthio-5'-AMP and therefore did not require the action of ADP, nor was there activation of platelet phospholipase. Platelet aggregation by heparin required a plasma cofactor different from the cofactor required for ristocetin.Fractionation of heparin yielded preparations that varied in molecular weight and, within a given molecular weight fraction, in affinity for antithrombin III. Fractions of high molecular weight (average 20,000) were more reactive with platelets than were fractions of low molecular weight (7,000). Anticoagulant activity did not parallel the platelet reactivity of heparin fractions. Among high molecular weight fractions, preparations of high or low antithrombin affinity were equally active in induction of platelet aggregation. In low molecular weight fractions, there was an inverse relationship between platelet reactivity and anticoagulant activity in normal platelet-rich plasma, but, in platelet-rich plasma depleted of antithrombin, low molecular weight fractions of high and low antithrombin affinity reacted equally with platelets. These results suggest that formation of an antithrombin-heparin complex protected platelets from aggregation by heparin.Selection of heparin fractions of low molecular weight and high antithrombin affinity may improve anticoagulant therapy and development of thromboresistant heparin-coated artificial materials.     

Immunopathogenesis and biomarkers of recurrent atrial fibrillation following ablation therapy in patients with preexisting atrial fibrillation

Introduction: Recurrent atrial fibrillation (RAF) following ablation therapy occurs in about 50% of patients. The pathogenesis of RAF is unknown, but is believed to be driven by atrial remodeling in the setting of background inflammation. Structural, electrophysiological and mechanical remodeling has been associated with atrial fibrillation (AF). Inflammation and fibrotic remodeling are the major factors perpetuating AF, as mediators released from the atrial tissues and cardiomyocytes due to mechanical and surgical injury could initiate the inflammatory process. In this article, we have critically reviewed the key mediators that may serve as potential biomarkers to predict RAF.

Areas covered: Damage associated molecular patterns, heat shock proteins, inflammatory cytokines, non-inflammatory markers, markers of inflammatory cell activity, and markers of collagen deposition and metabolism are evaluated as potential biomarkers with molecular treatment options in RAF.

Expert commentary: Establishing biomarkers to predict RAF could be useful in reducing morbidity and mortality. Investigations into the role of DAMPs participating in a sterile immune response may provide greater insight into the pathogenesis of RAF. Markers evaluating immune cell activity, collagen deposition, and levels of heat shock proteins show the greatest promise as potential biomarkers to predict RAF and develop novel therapies.     

Bioglass attenuates a proinflammatory response in mouse peritoneal endotoxicosis

Bioglass is a bioactive, resorbable ceramic particle that was developed to assure binding to living tissues. Bioglass is currently employed to fill osseus defects in oral surgery, and it possesses both unique anti-inflammatory and antimicrobial properties. In an effort to determine whether Bioglass may be useful as an adjunct anti-inflammatory device in local inflammatory processes, we examined whether exposure of the peritoneal cavity to Bioglass would induce a pro- or anti-inflammatory response, and then modulate a subsequent proinflammatory response to endotoxin. Three- to fifty-milligram doses of 5 pm Bioglass were administered intraperitoneally in C57BL/6 mice. Total leukocyte, myeloperoxidase, and cytokine levels in the peritoneal wash fluid were determined. In addition, the peritoneal cavity was preexposed to Bioglass, and was then subjected to a subsequent endotoxin administration. All doses of Bioglass were found to induce a significant peritoneal IL-6 response; however, Bioglass did not induce a TNF-alpha, IL-1alpha, IL-10, or a white cell recruitment into the peritoneal lavage fluid. Pretreatment of the peritoneal cavity with Bioglass produced a transient reduction in the proinflammatory response to endotoxin. We conclude that exposure to Bioglass produces an IL-6 response without concurrent expression of TNF-alpha or IL-1alpha. Bioglass appears to transiently suppress the inflammatory response to endotoxin, possibly through the early induction of IL-6. These findings suggest that Bioglass may offer a unique approach in modifying the inflammatory response in local tissue compartments.     

The Determination of Erythrocyte Folate Concentration Using a Two-Phase Ligand-binding Radioassay

The concentration of folate in erythrocyteswas determined using a two-phase ligand-binding radioassay procedure described previously for measuring serum folate. Themean (± SD) folate concentration in erythrocytes of 20 normal subjects was 210 ± 57ng/ml. In 12 patients clinically folatedeficient who had normal serum B₁₂concentration, the mean (± SD) erythrocytefolate was 71 ± 39 ng/ml. Incubation of thelysed erythrocytes for 2 hr prior to boilingincreased the radioassayable folate. Theradioassayable folate decreased rapidly ifthe whole blood was stored at 4°C withoutascorbate. Extracts of blood prepared withascorbate could be stored at -20°C forseveral days. The radioassayable concentration of erythrocyte folate was similarto the values obtained using Lactobacilluscasei when the concentration was 200 ng/ml or less. With values higher by L. casei,the radioassayable folate was significantlylower even though the normal and folate-deficient groups were distinctly separated.This radioassay provides a rapid and reliablemethod of measuring erythrocyte folate, aparameter which reflects folate stores morereliably than serum folate concentration.

Submitted on July 27, 1973 Accepted on August 20, 1973