Bipolar Stimulation of Cardiac Tissue Using an Anisotropic Bidomain Model

Bipolar Stimulation of the Cardiac Bidomain. Introduction: One of the fundamental electrophysiologic problems that has not yet been completely elucidated is the response of cardiac tissue to externally applied electric currents. A limited number of theoretical and experimental techniques has been used to study the electric behavior of cardiac tissue in the presence of stimulating currents, and to demonstrate that the anisotropy in the passive electrical properties of the tissue plays an important role in the genesis and propagation of the activation wave-front and the resulting potential distributions.
Methods and Results: In this work we have applied the finite element method to study the electric and magnetic fields produced by cardiac tissue in response to bipolar current injection, using a linear bidomain model to represent the tissue. We found that the transmembrane potential distribution close to the stimulus electrode has a rather complex geometrical pattern, with adjacent hyperpolarized and depolarized regions.
Conclusion: This behavior is consistent with previous theoretical and experimental results and may have implications in the study of electrical stimulation of cardiac tissue that are not apparent using other models.     

Developmental Toxicity of CI-921, an Anilinoacridine Antitumor Agent

CI-921, an anilinoacridine compound active against leukemicand solid tumors, was evaluated for potential developmentaltoxicity. Intravenous injections of CI-921 in dextrose weregiven to female Sprague-Dawley rats (0.1, 0.5, and 1.0 mg/kg)on Gestation Days (GD) 6–15 and to female New ZealandWhite rabbits (0.1, 1.0 and 2.0 mg/kg) on GD 6–18. Appropriatevehicle and untreated controls were included. Maternal and fetalparameters, including external, visceral, and skeletal malformationsand variations, were assessed. Treatment of rats with 1.0 mg/kgresulted in maternal toxicity, manifested as reduced body weightgain and food consumption during and after treatment. Reducedfetal body weight, an increased incidence of stunted fetuses,malformations of the axial and appendicular skeleton, microphthalmia,and an increased number of anatomical variations (includinganomalies of the axial skeleton and apparent hydronephrosis)also occurred in rats at 1.0 mg/kg. Treatment of rabbits resultedin no apparent maternal toxicity. However, reduced fetal bodyweight, agenesis of the azygous lobe of the lung, and an increasedincidence of variations of the axial skeleton occurred at 2.0mg/kg in rabbits. These results indicate that CI-921, at thehighest dose tested in each species, produced developmentaltoxicity in the presence of maternal toxicity in rats, but inthe absence of maternal toxicity in rabbits.     

The treatment of hypertension

1 A 'retrospective' of the development of the drug treatment of hypertension is presented from the early days of ganglion blockers to the present time together with a review of the evidence of benefit from treatment.
2 Current issues and debates are summarised including shortfalls in the control of hypertension in populations, difficulties surrounding the measurement of blood pressure, disagreement on the levels of blood pressure to treat, the goal blood pressures to aim at, issues surrounding lifestyle measures such as the low salt diet and low intensity exercise, and treatment with diuretics and with calcium antagonists.
3 A 'perspective' is presented on some avenues for progress in the years ahead. These will include the identification of genetic markers to determine the hypertensive individuals with the greatest risk of death and of cardiovascular complications.     

Randomized Evaluation of an Inflatable Femoral Artery Compression Device After Cardiac Catheterization

Mechanical femoral artery compression devices have several limitations. We compared a novel disposable beltheld pneumatic compression device to manual compression alone in 213 patients randomized into two equal groups. Both were comparable for age, gender, current therapy with aspirin (ASA) and warfarin, diameter of the arterial sheath, previous procedures via the same artery, procedure duration, and blood pressure. Manual compression time was 12 ± 3 minutes. Pneumatic compression was reduced during 60 minutes. Patient discomfort was assessed as none (82% vs 88%), mild (13% vs 8%), moderate (3% vs 4%), or severe (2% vs 0%) for the manual versus pneumatic group, respectively. Bleeding and hematoma occurred in 7.5% of patients with no difference between the treatment groups. However, manual compression was significantly more effective in the higher range of systolic blood pressure, and pneumatic in the lower range, with a cut point of approximately 170 mmHg. Predictors for bleeding were systolic blood pressure and dose of ASA. Among 113 patients with systolic blood pressure < 160 mmHg and low dose (75 mg) or no ASA, only / patient (0.9%) experienced bleeding while 31% of 16 patients with both elevated systolic blood pressure and high dose ASA (150–330 mg) bled. We conclude that pneumatic femoral artery compression does not reduce bleeding and hematoma compared with manual compression. The use of low dose (75 mg) or no ASA, as well as giving special attention to patients with elevated systolic blood pressure, may reduce the risk of bleeding after cardiac catheterization .     

DNA flow-cytometric analysis in colorectal cancer: A comparison of metastasizing and non-metastasizing tumours

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.