The Effect of Aspirin on Recurrent Fetal Loss in Experimental Antiphospholipid Syndrome

PURPOSE: To evaluate the effect of aspirin treatment upon fetal loss in mice with experimental antiphospholipid syndrome (APLS). MATERIALS AND METHODS: Experimental APLS was induced in pregnant mice by passive transfer of mouse monoclonal anticardiolipin antibody. The mice were treated with high (100μg/d) or low (10μg/d) does of aspirin, using vitaminC(100μg/d or 10μg/d)as a control. The mice were assessed for the presence of lupus anticoagulants (prolonged aPTT), thrombocytopenia, degree of fetal resorption rate and mean embryo and placental weights. RESULTS: The mice with APLS had a higher fetal resorption rate(45.7± 12.2% vs 2.5 ± 0.4%, P<0.001), reduced placenta mean weight(104 ± 8 mgvs 169 ±7mg, P<0.001), prolonged aPTT (94± 14sec vs 39±4sec, P<0.001), and reduced mean platelet count(597± 186 ± 10³/mm³vs 847±51 ± 10³/mm³,P<0.001). The groupof mice with APLS, who were treated with low-dose aspirin, had a lower resorption rate (11.1 ±9.3% vs 45.7±12.2%, P<0.001), a higher placenta mean weight (178 ± 8 mg vs 104 ± 8 mg, P<0.001), a higher mean embryo weight (1042 ± 134 mg vs 721±91 mg, P<0.001), and a lower aPTT (58±15 sec vs 94±14 sec, P, <0.001). Micewho were treated with high-dose aspirin also had a lower resorption rate, although not as much as in the low-dose aspirin group (34.2 ± 12.7% vs 45.7 ± 12.2%, P<0.001). CONCLUSION: Aspirin, especially in low dose, has a protective effect against obstetrical complications associated with experimental APLS.     

Endodontic management of molars with developmental anomalies

Summary. Rare reports of endodontic therapy in fused permanet molars appear in the literature, and these indicate the complexity of such cases. Three further cases are reported in this paper, establishing a conclusion of clinical value; all the root canals should be expected to emerge from one chamber, comprising one root canal system. This finding dismisses any attempts of 'partial' therapy in cases of posterior fusion. The variability in root canal systems in fused teeth makes it difficult to predict their configuration. Endodontic treatment of fused teeth calls for special efforts directed towards realizing and successfully managing their complex root canal systems.     

Mutations in Conserved Amino Acids in the KCNQ1 Channel and Risk of Cardiac Events in Type-1 Long-QT Syndrome

Background: Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage-gated potassium channel family are associated with an increased risk of cardiac events.
Methods and Results: The study population involved 492 LQT1 patients with 54 missense mutations in the transmembrane region of the KCNQ1 channel. The amino acid sequences of the transmembrane region of 38 human voltage-gated potassium channels were aligned. An adjusted Shannon entropy score for each amino acid residue was calculated ranging from 0 (no conservation) to 1.0 (full conservation). Cox analysis was used to identify independent factors associated with the first cardiac event (syncope, aborted cardiac arrest, or death). Patients were subcategorized into tertiles by their adjusted Shannon entropy scores. The lowest tertile (score 0–0.469; n = 146) was used as a reference group; patients with intermediate tertile scores (0.470–0.665; n = 150) had no increased risk of cardiac events (HR = 1.19, P = 0.42) or aborted cardiac arrest/sudden cardiac death (HR = 1.58, P = 0.26), and those with the highest tertile scores (>0.665; n = 196) showed significantly increased risk of cardiac events (HR = 3.32, P <0.001) and aborted cardiac arrest/sudden cardiac death (HR = 2.62, P = 0.04). The increased risk in patients with the highest conservation scores was independent of QTc, gender, age, and beta-blocker therapy.
Conclusions: Mutations in highly conserved amino acid residues in the KCNQ1 gene are associated with a significant risk of cardiac events independent of QTc, gender, and beta-blocker therapy.     

Risk Factors for Recurrent Heart Failure Events in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT‐II)

Risk Factors for Recurrent Heart Failure . Background: This study was designed to identify risk factors for recurrent heart failure (HF) events in patients with ischemic left ventricular dysfunction enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT‐II). Methods and Results: The Prentice, Williams, and Peterson (PWP) statistical model was utilized to identify and compare risk factors for 1 or ≥2 HF hospitalizations among 1,218 patients with ischemic left ventricular dysfunction enrolled in the MADIT‐II trial. Risk factors for a first HF hospitalization included treatment with an ICD (HR = 1.31; P = 0.05), New York Heart Association class >II (HR = 1.95; P < 0.001), female gender (HR = 1.38; P = 0.05), atrial fibrillation (HR = 1.90; P = 0.001), QRS >120 ms (HR = 1.41; P = 0.01), diabetes mellitus (HR = 1.51; P = 0.003), heart rate ≥80 (HR = 1.35; P = 0.04), diuretic therapy (HR = 1.82; P < 0.001), and the presence of prerenal azotemia (defined as blood urea nitrogen:creatinine >20; HR = 1.45; P = 0.01). In contrast, prerenal azotemia was the only risk factor that was independently associated with a significant increase in the risk of ≥2 HF hospitalizations (HR = 1.52; P = 0.027). The occurrence of 1 HF event after enrolment was associated with a 2.8‐fold (P < 0.001) increase in the risk of death, whereas after the occurrence of a second event there was a 6.7‐fold (P < 0.001) increase in the risk of subsequent mortality. Conclusions: In MADIT‐II, prerenal azotemia was the only significant and independent risk factor for HF progression after a first event, and recurrent HF was the most powerful predictor of mortality. These findings stress the importance of identifying risk factors for HF progression among patients who receive an ICD for primary prevention. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1217‐1223, November 2010)     

Leiomyosarcoma of the Right Atrium Masked by a Covering Thrombus: Conflicting Results of Echocardiography and Transvenous Biopsy—In Favor of Echocardiography

A 62-year-old woman was admitted for the evaluation of pedal edema and ascitis. Echocardiography revealed a right atrial (RA) mass invading the interatrial septum and extending into the inferior vena cava (IVC). Contrast enhanced computerized tomography scan excluded extravascular involvement. An organized thrombus was diagnosed by transvenous endomyocardial biopsy. The patient was treated with continuous intravenous heparin, and died soon after from hepatic failure. Postmortem histologic examination revealed a leiomyosarcoma surrounded by a thrombus involving RA, IVC, and hepatic veins. Endomyocardial biopsy played a misleading role that affected patient's management.     

Elevated growth hormone levels in patients with non-alcoholic chronic liver disease

High serum concentrations of growth hormone (GH) were found in five patients with chronic liver diseases, including auto-immune chronic active hepatitis (two cases), Budd-Chiari syndrome, primary biliary cirrhosis and hepatitis B virus associated cirrhosis. Mean levels of GH were 27.8 units (normal up to 5). In three patients elevated prolactin levels were also found (mean 37.3 units for two females, normal up to 20), and 36 units in one male (normal up to 9). No other endocrine disorders were found. Although the association of raised GH levels in patients with alcoholic cirrhosis is well known, its occurrence in patients with non-alcoholic chronic liver disease is not fully established. We describe the effect of the disease course, and steroid treatment on GH levels in one patient with auto-immune chronic active hepatitis, and propose possible mechanisms for this elevation.     

Studies on the Regulation of Hemopoietic Spleen Colonies

The in vivo intrasplenic cloning of haemopoietic cells was used as an experimental system for the study of some aspects concerned with the regulationof erythropoiesis. Experiments on the effects of polycythemia on the formationof erythroid clones demonstrated that the "feedback" suppression of such cloneswas inhibited if the polycythemic animals were kept under hypoxic conditions. Overloading with oxygen is, thus, an essential factor in the polycythemia-induced suppression of erythroid clones. Polycythemic animals whichwere transferred to hypoxic conditions for only 48 hours before the terminationof the experiment showed the formation of erythroid clones. Analysis of cloneformation following such short exposures to hypoxia suggests that the endogenous erythropoietin which had been functioning in this situation actednot upon the single clone-forming cell, but rather on small cell populationswhich derived from the clone-forming cells in the absence of erythropoietin.There is, therefore, an early, erythropoietin-independent phase of replicationof the clone-forming cells. The application of erythopoietin only during this"early" phase of replication resulted in the formation of erythroid clones, which,following the discontinuation of erythropoietin, disappeared from the spleen.Similar results were obtained when the action of endogenous erythropoietinwas terminated by subjecting animals to polycythemic conditions a few daysafter the injection of bone marrow. It appears that in both these cases thereduction in the number of spleen colonies following discontinuation of erythropoietin activity is due to the total maturation of the erythroid colonies,ending in the evacuation from the spleen of the mature red blood cells. Thedifferentiation of the cloned cells is, thus, causally related to the cessation ofthe replicating effect of erythropoietin.

Submitted on June 22, 1966 Accepted on November 24, 1966