Reproducibility of Computerized Measurements of QT Interval from Multiple Leads at Rest and During Exercise

Background: Accurate measurement of the QT interval is important for diagnosing long QT syndrome (LQTS), and in research on determinants of ventricular repolarization time. We tested automatic analysis of QT intervals from multiple ECG leads on chest. Methods: Eleven healthy volunteers and 10 genotyped LQTS patients were tested at rest and during exercise with a bicycle ergometer twice 1–31 months apart. Electrocardiograms were recorded with the body surface potential mapping system, and 12 precordial channels were selected for analysis. Averaged QT peak and QT end intervals were determined with an automated algorithm, and the difference QT end minus QT peak (Tp‐e) was calculated. Repeatability was assessed by coefficient of variation (CV) between measurements. Results: Within one test at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for QT end and 2.9% for QT peak interval. The CV of Tp‐e interval was 10.2% at rest, and 9.3% in exercise test. Reproducibility was comparable between healthy subjects and LQTS patients. Conclusions: The BSPM system with automated analysis produced accurate and highly repeatable QT interval measurements. Reproducibility was adequate also over prolonged time periods both at rest and in exercise stress test. The method can be applied in studying duration of ventricular repolarization time in different physiologic and pharmacologic interventions.     

Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves.

AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.     

Polymeric genes MEL8, MEL9 and MEL10 — new members of α-galactosidase gene family in Saccharomyces cerevisiae

Summary We used a combination of genetic hybridization analysis and electrokaryotyping with radioactively labelled MEL1 gene probe hybridization to isolate and identify seven polymeric genes for the fermentation of melibiose in strain CBS 5378 of Saccharomyces cerevisiae (syn. norbensis). Four of the MEL genes, i.e. MEL3, MEL4, MEL6 and MEL7, were allelic to those found in S. cerevisiae strain CBS 4411 (syn. S. oleaginosus) whereas three genes, i.e. MEL8, MEL9 and MEL10 occupied new loci. Electrokaryotyping showed that all seven MEL genes in CBS 5378 were located on different chromosomes. The new MEL8, MEL9 and MEL10 genes were found on chromosomes XV, X/XIV and XII, respectively.     

Herpes zoster infection with trigeminal and facial nerve involvement

In most cases, herpes zoster (shingles) infections are benign and self-limited, requiring no treatment. However, if patients are elderly or immuno-compromised, they are at increased risk of complications such as visceral dissemination, cranial and nerve palsies, ophthalmic zoster, and postherpetic neuralgia. We present a case of herpes zoster infection complicated by both motor and sensory involvement in an elderly man.     

Prognostic value of various staging and grading systems in proximal colon cancer.

OBJECTIVE: To compare the ability of various methods of staging and grading to predict survival in proximal colon cancer. DESIGN: Retrospective study. SETTING: University hospital, Finland. SUBJECTS: 153 patients with primary proximal colon cancer. MAIN OUTCOME MEASURES: Staging by four classification systems, grading by two grading systems, and survival analysis based on Kaplan-Meier survival curves. RESULTS: In all staging systems the survival curves of different stages differed significantly from each other. The modified Dukes' classification was still the best predictor of survival. Grade of tumours had no significant effect on long term survival, but short term survival was affected adversely by the presence of anaplastic tissue. Tumours with no mucin had a worse prognosis than those that produced mucin. All staging methods were superior to either of the histological grading systems tested as prognosticators. Tumour depth correlated with the operator's clinical impression of radicality of operation, and also predicted survival. CONCLUSION: The clinicopathological modified Dukes' staging system was the most powerful prognosticator in proximal colonic cancer and its use in clinical practice should continue. Even a small amount of anaplastic tissue (> or = 5%) had an adverse effect on short term survival.     

Patency of the infarct-related coronary artery — a pertinent factor in late recovery of myocardial fatty acid metabolism among patients receiving thrombolytic therapy?

The decrease in mortality among patients receiving thrombolytic therapy for myocardial infarction is greater than would be expected from the improvement in left ventricular contractile function alone; thus some additional advantage of recanalization of the infarctrelated coronary artery probably exists. Changes in the post-infarction myocardial metabolic state with respect to artery patency have not been studied with a gamma camera previously. A single-photon emission tomography scan using the fatty acid analogue para-¹²³I-iodophenylpentadecanoic acid was performed at rest before hospital discharge on nine patients with first anterior myocardial infarction. All patients had received intravenous thrombolytic therapy at the beginning of the insult. The semiquantitative analysis of the left ventricle included a total of 44 segments in each patient. The test was repeated 3 months later, with the patients divided into two groups: six patients had an angiographically patent left anterior descending coronary artery (group A), and three an occluded artery (group B). In group A the number of myocardial segments with abnormal (<70% of maximum) fatty acid uptake was initially 20.2±4.7 (mean±SD) and was reduced to 11.3±6.1 during the follow-up (95% confidence interval of the decrease 16.0–1.7 segments). In group B the number of these aberrant segments was fairly constant (21.7±13.1, initial test, and 21.3±13.3, retest). Our preliminary results suggest that even when thrombolytic therapy fails to prevent myocardial infarction, myocardial fatty acid metabolism has a better change of recovering if the relevant coronary artery has regained its patency. This finding emphasizes the need for further study to establish whether a direct link exists between myocardial metabolic state and patient survival after infarction.     

Levels of adrenodoxin, NADPH-cytochrome P-450 reductase and cytochromes P-45011 beta, P-45021, P-450scc, in adrenal zona fasciculata-reticularis tissue from androgen-treated rats

Treatment of rats with methylandrostenediol (MAD), an anabolic androgen, caused a profound reduction (65%) in the level of cytochrome P-450 11 beta in rat adrenocortical mitochondria as measured by immunoblots using a specific antibody. The decreases in mitochondrial cytochrome P-450scc (15%) and adrenodoxin (20%) were much less than that observed for cytochrome P-45011 beta. A 35% decrease in adrenal microsomal cytochrome P-450 21 and NADPH-cytochrome P-450 reductase levels was brought about by the treatment with MAD. The data establish that the preferential decrease in adrenal steroid 11 beta-hydroxylase activity associated with androgen treatment results from a decrease in cytochrome P-450 11 beta. This is consistent with the role of 11-deoxycorticosterone in the pathogenesis of androgen-induced hypertension in rats.     

Meningococcal disease in the United States--1986. Meningococcal Disease Study Group

Active surveillance for invasive meningococcal disease was conducted during 1986 and 1987 in six areas of the United States with a total population of approximately 34 million persons. The incidence of meningococcal disease was 1.3:10(5). The highest incidence of disease among the surveillance areas was in Los Angeles County (1.65:10(5). Neisseria meningitidis serogroups B and C caused about equal amounts of disease, which reflects a recent increase in the incidence of group C disease. Group C caused more than half of the cases of meningococcal disease in Los Angeles and Tennessee but less than one-third of the cases in Missouri and Oklahoma. Multilocus enzyme electrophoresis demonstrated that a group of closely related isolates of N. meningitidis was prevalent in Los Angeles during the surveillance period and was associated with an increased incidence of meningococcal disease there.