Electrocardiographic and Clinical Predictors of Torsades de Pointes Induced by Almokalant Infusion in Patients with Chronic Atrial Fibrillation or Flutter: A Prospective Study

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 ± 114 vs 443 ± 54 ms [mean ± SD], P < 0.01), a larger precordial QT dispersion (50 ± 74 vs 27 ± 26 ms, P < 0.05), and a lower T wave amplitude (0.12 ± 0.22 vs 0.24 ± 0.16 mV. P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 ± 26 vs 489 ± 74 ms, P < 0.001), a larger QT dispersion in precordial (82 ± 7 vs 54 ± 52 ms, P < 0.01) and extremity leads (163 ± 0 vs 40 ± 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.     

The effect of indomethacin on cerebral blood flow and oxygen consumption in the rat at normal and increased carbon dioxide tensions

The effect of the fatty acid cyclo-oxygenase inhibitor indomethacin on cerebral blood flow (CBF) and the metabolic rate for oxygen (CMRO₂) was studied in paralyzed and artificially ventilated rats. In normocapnic animals, the drug (10 mg·kg^-1i. v.) reduced CBF to 50% of control without a measurable effect on CMRO₂. During hypercapnia (Pa_CO2 70–80 mmHg) the increase in CBF was reduced by about 80% but CMRO₂ remained unchanged. Autoradiographic evaluation of local CBF in 20 brain structures indicated that the reduction in CBF was relatively uniform throughout the brain. Dose response curves showed that an effect on CBF was evident already at an indomethacin dose of 1 mg·kg^-1 and maximal effects were obtained with 3–5 mg·kg^-1. Following i. v. injection of the drug reduction in CBF was observed already after 10 s and the full response occurred after 1–2 min. It is concluded that metabolites of arachidonic acid, possibly mainly prostacyclin, are powerful modulators of normal cerebrovascular tone, and help to mediate the CBF response to increased CO₂ tensions. However, since indomethacin does not modify the circulatory response in other conditions with increased CBF these substances do not qualify as general coupling factors controlling CBF in physiological or pathological states.     

Measurement of Ventilation and Respiratory Mechanics during Continuous Positive Airway Pressure (CPAP) Treatment in Infants

ABSTRACT. A new method has been evaluated for measuring ventilation and lung mechanics in spontaneously breathing infants by means of a face chamber. Airway flow is measured with a pneumotachograph inserted between the face chamber and a stable pressure source. Oesophageal pressure is measured via a water-filled oesophageal catheter. The method is suitable for use in conjunction with continuous positive airway pressure (CPAP) treatment in neonatal intensive care. A flat frequency response curve up to 15 Hz for the two measuring systems (i.e., airway flow and oesophageal pressure), and a time shift between the two respective signals of less than 2 msec are prerequisites for correct evaluation of respiratory mechanics. In preterm infants with chest distortion, the inhomogeneity of pleural pressure affects the significance of resistance and compliance values, as calculated from oesophageal pressure. Supra-diaphragmatic pressure variations reflect the resistive and elastic load on the diaphragm exerted by the lungs and thorax. Thus, oesophageal pressure is still useful in studies of respiratory mechanics in preterm infants.     

Mechanisms of Pancreatic B-Cell Degeneration during the Course of Insulin-dependent Diabetes Mellitus

ABSTRACT. This paper presents a review of different mechanisms possibly responsible for the degeneration of the pancreatic B-cell in insulin-dependent diabetes mellitus. The genetic dependence probably located in the HLA DR-locus of the sixth chromosome and its role in an autoimmune reaction against antigenieally altered pancreatic B-cells is discussed. The actions of alloxan and streptozotacin in the induction of experimental diabetes, as models for postulated human B-cytotoxins, are described.     

Erythropoiesis: Correlations Between Iron Status Markers During Normal Pregnancy in Women with and without Iron Supplementation

The aim was to evaluate relationships between iron status markers (haemoglobin, erythrocyte indices, serum iron, serum transferrin, serum transferrin saturation, serum ferritin) in normal pregnancy. Iron status markers were measured at 4-week-intervals during pregnancy and postpartum in 120 healthy women; 62 had daily treatment with tablets containing 66 mg ferrous iron, 58 were treated with placebo. Placebo-treated: Ferritin displayed positive correlations with transferrin saturation during 2nd and 3rd trimester. There were positive correlations between ferritin, erythrocyte MCV and MCH during 2nd and 3rd trimester and postpartum. Prior to delivery and postpartum, ferritin demonstrated positive correlations with haemoglobin. Transferrin saturation showed positive correlations with MCV, MCH and MCHC during 2nd and 3rd trimester and postpartum. Transferrin saturation displayed positive correlations with haemoglobin prior to delivery and postpartum. Iron-treated: In general, there were no correlations between iron status markers. Positive correlations appeared postpartum between ferritin, transferrin saturation and MCHC but not with haemoglobin. Transferrin saturation showed a positive correlation with MCH postpartum, but not with haemoglobin. Conclusion: The patterns of relationships in placebo-treated women were consistent with iron deficient erythropoiesis.     

Erythropoiesis: Short Report: Translation of Analysis Results between Serum Ferritin Assays, Ferritin RIA AmershamTM and Abbott AxSYMTM Ferritin

The serum ferritin assays, Ferritin RIA Amersham(TM) and Abbott AxSYM(TM) Ferritin were compared in order to translate values from one assay to the other. Serum ferritin was analysed with both assays in 102 samples. Logarithmic transformation of the results was performed in order to stabilize the variance. The relationship between the untransformed values was most exactly expressed by a proportionality: AxSYM Ferritin = 0.873 * RIA Ferritin. Due to this proportionality, the numerical difference between the assays increases with the ferritin concentration, although the percentage difference between the assays remains constant.     

Emergence of fluoroquinolone‐resistant clonal group A: clonal analysis of Norwegian and Russian E. coli isolates

Strand L, Jenkins A, Grude N, Allum A‐G, Mykland H‐C, Nowrouzian FL, Kristiansen B‐E. Emergence of fluoroquinolone‐resistant clonal group A: clonal analysis of Norwegian and Russian E. coli isolates. APMIS 2010; 118: 571–77. We describe a study of urinary tract and intestinal isolates of Escherichia coli from Norway and Russia using automated ribotyping, single nucleotide polymorphism analysis for clonal group A (CgA) supplemented with phylogrouping, virulence gene profiling and resistance profiling. CgA comprised 19% of the Norwegian UTI isolates from 2001. Two highly multiresistant fluoroquinolone‐resistant CgA isolates were found. Ribotypes clustered into four major and six minor groups (ribogroups). Fluoroquinolone‐resistant isolates and phylogroups A and B1 were associated with ribogroup ^RA. Ribogroup ^RB predominated among Russian UTI isolates and was predominantly phylogroup A and depleted in P‐fimbriae. Ribogroup ^RC predominated among Norwegian UTI isolates and was rich in virulence factors (S‐fimbriae, haemagglutinin and haemolysin) and predominantly phylogroup B2 and D. Ribogroup ^RG was associated with CgA and predominantly phylogroup D. Ribogroups ^RD, ^RE and ^RF had too few members for statistical analysis. The correlation between ribotype and phylogenetic group was not as strong as reported in other studies.