Computer simulation of supraventricular tachycardia with the Wolff-Parkinson-White syndrome using three-dimensional heart models

Supraventricular tachycardias with the Wolff-Parkinson-White (WPW) syndrome have been successfully simulated using a newly developed simulation system. The heart model, including atria and ventricles, was constructed of about 50,000 discrete elements (model cells) in three dimensions with 1.5-mm spatial resolution. The model cells covered all of the types of cells in the actual heart, including the normal myocardium, special conduction system and abnormal cells, such as the bundle of Kent (accessory pathway) and ectopic pacemaker (premature beat). Different model cells were specified by their electrophysiologic parameters, such as action potential, refractory period, and conduction velocity. The WPW syndrome was simulated by setting an accessory pathway between the right atrium and ventricle. Based on this model a premature atrial beat was introduced, which initialized the tachycardia. By adjusting the parameters, three types of reciprocal supraventricular tachycardia were simulated with the reentry circuits (1) formed anterogradely by the A-V node and retrogradely by the accessory pathway, (2) formed anterogradely by the accessory pathway and retrogradely by the A-V node, and (3) confined within the A-V node. Time relations for initializing and maintaining the tachycardias were evaluated. The simulated ECGs were in good agreement with the clinical findings.     

Heart rate at onset and termination of paroxysmal atrial fibrillation in apparently healthy subjects

Eighteen paroxysms were documented on Holter electrocardiogram both at the onset and the termination of paroxysmal atrial fibrillation in 14 apparently healthy subjects. There were large inter- and intraindividual variations and no definite trend was observed in the time and duration of paroxysms. Heart rate at the onset of paroxysms was consistently higher than that at sinus rhythm immediately before atrial fibrillation started. There were 2 patterns in the sequence of heart rate during paroxysms. One was an almost constant heart rate during paroxysms, and the other was a trend toward a decrease in heart rate from the onset to the termination of paroxysms. The duration of paroxysms was within 2 hours in the former group and more than 2 hours in the latter group. There was a reverse correlation between heart rate at the termination of paroxysms and their duration.     

Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan

Background  Matrix metalloproteinases (MMPs) are a family of enzymes that degrade most macromolecules making up the extracellular matrix. MMPs are involved in not only the gastric mucosal inflammatory response but also the pathogenesis of Helicobacter pylori-associated diseases. In the renin-angiotensin system, chymase (CMA) is related to gastric carcinogenesis and angiogenesis in H. pylori-infected patients. We aimed to clarify the association of MMP-7-181 and CMA/B polymorphisms with susceptibility to gastric cancer and cancer progression in H. pylori-infected patients. Methods  We assessed the MMP-7-181 and CMA/B polymorphisms in H. pylori-positive patients with gastric cancer (n = 160), gastric ulcer (n = 157), duodenal ulcer (n = 121), and H. pylori-positive gastritis alone as controls (n = 156). Results  For gastric cancer risk, the age-and sex-adjusted odds ratio (OR) of the MMP-7-181 G allele carrier relative to the A/A genotype was significantly increased [OR, 2.32; 95% confidence interval (CI), 1.24–4.35], especially in patients with noncardia cancer (OR, 2.31; 95% CI, 1.22–4.36) and those with clinical stage III or IV cancer (OR, 3.66; 95% CI, 1.54–8.73). Carriage of the CMA/B A allele was significantly associated with gastric cancer development (OR, 1.73; 95% CI, 1.10–2.71). Simultaneous carriage of both the MMP-7-181 G allele and the CMA/B A allele dramatically increased the gastric cancer risk (OR, 8.18; 95% CI, 2.79–23.93). Conclusions  In Japan, carriage of the MMP-7-181 G allele and of the CMA/B A allele were each associated with an increased risk for H. pylori-related noncardia gastric cancer development. MMP-7-181 and CMA/B genotyping tests might be useful tools for screening for individuals with higher gastric cancer risk.     

Significant effect of a pre-exercise high-fat meal after a 3-day high-carbohydrate diet on endurance performance

We investigated the effect of macronutrient composition of pre-exercise meals on endurance performance. Subjects consumed a high-carbohydrate diet at each meal for 3 days, followed by a high-fat meal (HFM; 1007 ± 21 kcal, 30% CHO, 55% F and 15% P) or high-carbohydrate meal (HCM; 1007 ± 21 kcal, 71% CHO, 20% F and 9% P) 4 h before exercise. Furthermore, just prior to the test, subjects in the HFM group ingested either maltodextrin jelly (M) or a placebo jelly (P), while subjects in the HCM ingested a placebo jelly. Endurance performance was measured as running time until exhaustion at a speed between lactate threshold and the onset of blood lactate accumulation. All subjects participated in each trial, randomly assigned at weekly intervals. We observed that the time until exhaustion was significantly longer in the HFM + M (p < 0.05) than in HFM + P and HCM + P conditions. Furthermore, the total amount of fat oxidation during exercise was significantly higher in HFM + M and HFM + P than in HCM + P (p < 0.05). These results suggest that ingestion of a HFM prior to exercise is more favorable for endurance performance than HCM. In addition, HFM and maltodextrin ingestion following 3 days of carbohydrate loading enhances endurance running performance.     

Synergistic effect of heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin and X-rays, but not carbon-ion beams, on lethality in human oral squamous cell carcinoma cells

The purpose of this study is to clarify the effect of a heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in combination with X-rays or carbon-ion beams on cell killing in human oral squamous cell carcinoma LMF4 cells. Cell survival was measured by colony formation assay. Cell-cycle distribution was analyzed by flow cytometry. Expression of DNA repair-related proteins was investigated by western blotting. The results showed 17-AAG to have synergistic effects on cell lethality with X-rays, but not with carbon-ion beams. The 17-AAG decreased G(2)/M arrest induced by X-rays, but not by carbon-ion beams. Both X-ray and carbon-ion irradiation up-regulated expression of non-homologous end-joining-associated proteins, Ku70 and Ku80, but 17-AAG inhibited only X-ray-induced up-regulation of these proteins. These results show that 17-AAG with X-rays releases G(2)/M phase arrest; cells carrying misrepaired DNA damage then move on to the G(1) phase. We demonstrate, for the first time, that the radiosensitization effect of 17-AAG is not seen with carbon-ion beams because 17-AAG does not affect these changes.