Toll-like receptor signalling associated with immunomodulation of umbilical cord-derived mesenchymal stem cells in mice with systemic lupus erythematosus.

With potent immunomodulatory activities, mesenchymal stem cells (MSCs) have the potential to be a beneficial treatment option for diseases with aberrant immune responses such as systemic lupus erythematosus (SLE). However, the underlying mechanisms remain largely unknown. Here, we used NZBWF1 mice as a SLE animal model to examine immunomodulation of MSCs as well as to assess the role of Toll-like receptor signalling in this circumstance. We found that mice receiving MSCs had a significant decrease in severity of proteinuria at 20 and 22 weeks of age (p = 0.009 and p = 0.022, respectively). Serum anti-dsDNA levels were significantly lower compared with the control group (p = 0.016 and p = 0.036, respectively). C3 and C4 levels were significantly higher at 22 weeks of age (p = 0.046 and p = 0.016, respectively). Altered expression of inflammation-associated cytokine profiles in the serum was also noted in mice receiving MSCs. Down-regulation of myeloid differentiation factor 88 (MyD88)-nuclear factor-κB (NF-κB) signalling in the liver was demonstrated by quantitative polymerase chain reaction, ELISA and Western blotting. In addition to demonstrating the beneficial effects of MSC treatment in NZBWF1 mice, our study provided the first evidence for the association of MyD88-NF-κB signalling and MSC-mediated immunomodulation in this disease.

Minimally invasive right colectomy with transrectal natural orifice extraction: could this be the next step forward?

BACKGROUND: The transvaginal natural orifice specimen extraction (NOSE) approach for right-side colon surgery has been proven to exhibit favorable short-term outcomes. However, thus far, no study has reported the advantages of transrectal NOSE for right-side colon surgery. The aim of this study was to compare the technical feasibility, safety, and short-term outcomes of minimally invasive right hemicolectomy using the transrectal NOSE method and those of conventional mini-laparotomy specimen extraction. METHODS: A study was conducted on consecutive patients who had minimally invasive right hemicolectomy either for malignancy or benign disease at Chang Gung Memorial Hospital, Linkou, Taiwan, between January 2017 and December 2018. The patients were divided into two groups: conventional surgery with specimen extraction using mini-laparotomy and NOSE surgery. Surgical outcomes, including complications, postoperative short-term recovery, and pain intensity, were analyzed. RESULTS: We enrolled 297 patients (151 males, mean age 64.9 ± 12.8 years) who had minimally invasive right hemicolectomy. Of these 297 patients, 272 patients had conventional surgery with specimen extraction through mini-laparotomy and 25 patients had NOSE surgery (23 transrectal, 2 transvaginal). The diagnosis of colon disease did not differ significantly between the conventional and NOSE groups. Postoperative morbidity and mortality rates were comparable. The postoperative hospital stay was significantly (p = 0.004) shorter in the NOSE group (median 5 days, range 3-17 days) than in the conventional group (median 7 days, range 3-45 days). Postoperative pain was significantly (p = 0.026 on postoperative day 1 and p = 0.002 on postoperative day 2) greater in the conventional group than in the NOSE group. CONCLUSIONS: NOSE was associated with acceptable short-term surgical outcomes that were comparable to those of conventional surgery. NOSE results in less postoperative wound pain and a shorter hospital stay than conventional surgery. Larger studies are needed.

Detection of viable antibiotic-resistant/sensitive Acinetobacter baumannii in indoor air by propidium monoazide quantitative polymerase chain reaction.

Acinetobacter baumannii represents a significant cause of nosocomial infections. Therefore, we combined real-time quantitative polymerase chain reaction (PCR) with the propidium monoazide (PMA-qPCR) to assess the feasibility of detecting viable, airborne A. baumannii. The biological collection efficiencies of three samplers for collecting airborne A. baumannii were evaluated by PMA-qPCR in a chamber study. After sampling, the effects of storage in collection fluid on A. baumannii were evaluated. The results showed that the culturable ratio of A. baumannii measured using the culture method was significantly correlated with the viable ratio measured using PMA-qPCR, but was not significantly correlated with the qPCR results. It was indicated that the AGI-30 impinger and the BioSampler were much more effective than the Nuclepore filter sampler for collecting airborne A. baumannii. The storage temperature was critical for aerosol samples, as the loss of viable A. baumannii was minimized when the PMA-bound DNA was stored at -20°C or if the collected cells were stored at 4°C and subsequently processed by PMA-qPCR within 1 month. The PMA-qPCR method was also to distinguish between colistin-sensitive and colistin-resistant A. baumannii, and no colistin-sensitive A. baumannii was detected by PMA-qPCR upon treatment of the BioSampler collection medium with 2 µg/ml colistin for 5 min.

Risk of adolescent offspring's completed suicide increases with prior history of their same-sex parents' death by suicide.

BACKGROUND: To investigate the risk of completed suicide in offspring during adolescence in relation to prior history of the same-sex parent's death by suicide and other causes. METHOD: A total of 500 adolescents who died by suicide at age 15-19 years between 1997 and 2007 were identified from the Taiwan Mortality Registration (TMR). For each case, 30 age- and time-matched controls were selected randomly from all adolescents registered in the Taiwan Birth Registry (TBR). A multivariate conditional logistic regression model was used to assess the risk of adolescent completed suicide in relation to their same-sex parent. RESULTS: Adolescent suicide risk was positively associated with both paternal [odds ratio (OR) 5.38, 95% confidence interval (CI) 2.17-13.33] and maternal suicide (OR 6.59, 95% CI 1.82-23.91). The corresponding risk estimates associated with paternal and maternal deaths from non-suicidal causes were much lower, at 1.88 and 1.94 respectively. The risk of suicide in male adolescents was significantly associated with prior history of paternal death by suicide (OR 8.23, 95% CI 2.96-22.90) but not of maternal death by suicide (OR 3.50, 95% CI 0.41-30.13). On the other contrary, the risk of suicidal death in female adolescents was significantly associated with prior history of maternal suicide (OR 9.71, 95% CI 1.89-49.94) but not of paternal suicide (OR 2.42, 95% CI 0.30-19.57). However, these differences did not reach statistical significance. CONCLUSIONS: Although limited by sample size, our study indicates that adolescent offspring suicidal death is associated with prior history of their same-sex parent's death by suicide.

Empirical Selection of Informative Microsatellite Markers within Co-ancestry Pig Populations Is Required for Improving the Individual Assignment Efficiency.

The Lanyu is a miniature pig breed indigenous to Lanyu Island, Taiwan. It is distantly related to Asian and European pig breeds. It has been inbred to generate two breeds and crossed with Landrace and Duroc to produce two hybrids for laboratory use. Selecting sets of informative genetic markers to track the genetic qualities of laboratory animals and stud stock is an important function of genetic databases. For more than two decades, Lanyu derived breeds of common ancestry and crossbreeds have been used to examine the effectiveness of genetic marker selection and optimal approaches for individual assignment. In this paper, these pigs and the following breeds: Berkshire, Duroc, Landrace and Yorkshire, Meishan and Taoyuan, TLRI Black Pig No. 1, and Kaohsiung Animal Propagation Station Black pig are studied to build a genetic reference database. Nineteen microsatellite markers (loci) provide information on genetic variation and differentiation among studied breeds. High differentiation index (FST) and Cavalli-Sforza chord distances give genetic differentiation among breeds, including Lanyu's inbred populations. Inbreeding values (FIS) show that Lanyu and its derived inbred breeds have significant loss of heterozygosity. Individual assignment testing of 352 animals was done with different numbers of microsatellite markers in this study. The testing assigned 99% of the animals successfully into their correct reference populations based on 9 to 14 markers ranking D-scores, allelic number, expected heterozygosity (HE) or FST, respectively. All miss-assigned individuals came from close lineage Lanyu breeds. To improve individual assignment among close lineage breeds, microsatellite markers selected from Lanyu populations with high polymorphic, heterozygosity, FST and D-scores were used. Only 6 to 8 markers ranking HE, FST or allelic number were required to obtain 99% assignment accuracy. This result suggests empirical examination of assignment-error rates is required if discernible levels of co-ancestry exist. In the reference group, optimum assignment accuracy was achievable achieved through a combination of different markers by ranking the heterozygosity, FST and allelic number of close lineage populations.

Mycophenolate mofetil alleviates lupus nephritis through urokinase receptor signaling in a mice model.

Lupus nephritis (LN) is usually associated with widespread effacement of the podocytes' foot processes leading to proteinuria. Induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via promoting podocytes' motility and kidney permeability in the glomerulus. Very little is known about uPAR signaling in LN. Mycophenolate mofetil (MMF), an immunosuppressive agent, efficiently modulates the development of LN in humans and mice, but there are no data concerning the direct uPAR involvement on podocytes in LN. The MMF efficiency and uPAR involvement signaling in NZB×NZW F1 lupus-prone mice were examined by proteinuria, renal function and pathology, immune complex deposits, and uPAR expression of podocytes by immunofluorescence staining and quantitative RT-PCR. After MMF treatment, the proteinuria (p < 0.01), BUN level (p < 0.05) and immunodeposition in glomeruli (p < 0.001) were significantly improved. Most important, the renal uPAR mRNA levels (p < 0.001) and uPAR protein level of podocytes (p < 0.001) were significantly reduced. The beneficial effect of MMF on LN could be attributed, at least in part, to the inhibition of uPAR expression in podocytes. These findings demonstrated uPAR could have potential as a predictive index for response to LN therapeutics.

Effect modification by parental education on the associations of birth order and gender with learning achievement in adolescents.

BACKGROUND: A child's gender and ordinal position within a family have varied implications on his or her personality and cognitive development. However, little is known about whether or not parental educational level may moderate the effects of birth order and gender. METHODS: Basic Competence Test (BCT) scores of 290,588 young adolescents aged 15-16 years in Taiwan were analysed. Parental educational level was calculated as the highest educational attainment of the subjects' parents. The multiple linear regression model was used to assess the modification effects of parental educational levels on the associations of interest. RESULTS: After controlling for covariates, we noted a clear inverse relationship between birth order and BCT scores in Mandarin, Mathematics and Science. Additionally, boys had significantly lower mean scores in Mandarin, but had significantly higher mean scores in both Mathematics and Science. We also found the significant interactive effects of birth order, gender and parental educational attainment on BCT scores, in which the birth order and gender effects were more evident in higher-educated families than in lower-educated ones. CONCLUSIONS: This large cohort study confirmed that both birth order and gender may pose independent influences on BCT scores; moreover, such influences are significantly modified by parental educational attainment.

X-ray microscopy and tomography detect the accumulation of bare and PEG-coated gold nanoparticles in normal and tumor mouse tissues.

We demonstrate that, with appropriate staining, high-resolution X-ray microscopy can image complicated tissue structures--cerebellum and liver--and resolve large or small amounts of Au nanoparticles in these tissues. Specifically, images of tumor tissue reveal high concentrations of accumulated Au nanoparticles. PEG (poly(ethylene glycol)) coating is quite effective in enhancing this accumulation and significantly modifies the mechanism of uptake by reticuloendothelial system (RES) organs.

Validating the Cerebral Palsy Quality of Life for Children (CP QOL-Child) questionnaire for use in Chinese populations.

The purpose of this study was to examine the psychometric properties of the Chinese version of Cerebral Palsy Quality of Life for Children (CP QOL-Child) questionnaire. We performed forward (into Chinese) and backward translation of the CP QOL-Child for: (1) the primary caregiver form (for parents of children with CP aged 4-12 years); and (2) the child self-report form (for children with cerebral palsy aged 9-12 years). Psychometric properties assessed included test-retest reliability, internal consistency, item discrimination, construct validity, and concordance between the forms of questionnaire. The Chinese CP QOL-Child was completed by 145 caregivers and 44 children. Excellent test-retest reliability and internal consistency were obtained. Item discrimination analysis revealed a majority of the items have moderate to good discriminating power. Confirmatory factor analysis demonstrated distinguishable domain structure as on the original English version. Significant associations were found between lower QOL and more severe motor disability. Consistent with the English version, the highest correlation between the primary caregiver and child forms on QOL was in the domain of functioning. Results of this study indicate that the Chinese CP QOL-Child appears to be valid for use in Mandarin-Chinese speaking children with cerebral palsy.

High-throughput gender identification of Accipitridae eagles with real-time PCR using TaqMan probes.

The objective was to develop high-throughput gender identification of eagles. Based on BLAST and alignment analyses, the CHD-Z and CHD-W sequences of nine species of eagles were highly homologous with Spilornis cheela hoya (S. c. hoya); therefore, TaqMan probes were designed to target their CHD-ZW-common and CHD-W-specific regions. In S. c. hoya, genders were identified using TaqMan-based, real-time PCR (amplified by P2/P8 primers); this method was validated with anatomically confirmed controls (one of each gender). Both genders had high intensities of the HEX-labeled (CHD-ZW-common) probe, whereas only females had high intensity of the FAM-labeled (CHD-W-specific) probe. The sequence of the CHD-W-specific probe designed for S. c. hoya was completely homologous with the CHD-W-specific region in Circaetus gallicus, Gyps indicus, and Gyps bengalensis, and was only one nucleotide different from those of Accipiter nisus, Spizaetus nipalensis, Aquila chrysaetos, Circus spilonotus, and Milvus migrans. For the CHD-ZW-common probe, all species listed were completely conserved. Using real-time PCR software, we established auto-calling of the genders of 15 individuals of S. c. hoya. In conclusion, this method provided accurate, high-throughput gender identification for S. c. hoya, and has considerable potential for identifying the gender of several related species of eagles.

New-onset atrial fibrillation-related ischemic stroke occurring after hospital discharge in septicemia survivors.

BACKGROUND: Sepsis will induce stroke, new-onset atrial fibrillation (AF) increase ischemic stroke (IS) in in-hospitalization and long-term period after sepsis. Physicians must alert this condition and given suitable treatment. AIM: The associated of IS and new-onset AF in septicemia survivors after discharge have to be evaluated. DESIGN: The inpatient data was used of the Taiwan National Health Insurance Database (NHIRD) in 2010. We identified patients suffered their first occurrence of septicemia (International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] is 038, 003.1, 036.1) and excluded less than 18 years old. Patients had AF (ICD-9-CM to 427.3×) during the same admission or after septicemia hospitalization discharged were defined as new-onset AF. The outcome was IS happened after septicemia discharge (ICD-9-CM as 433-437). METHODS: The factors related to IS after septicemia survival were established using multivariate logistic regression with forward stepwise selection. RESULTS: There were 1286 new-onset AF and 1026 IS happened after septicemia discharge. The crude odds ratio (OR) were 3.88 (95% confidence interval [C.I.]: 1.69-8.89) and 1.62 (95% C.I.: 1.14-2.3) in middle-aged and elderly septicemia survivors with new-onset AF induced IS. The risk of IS after septicemia survivors was noticed adjusted OR 1.74 (95% C.I.: 1.26-2.41) for new-onset AF. CONCLUSION: The middle-aged and elderly septicemia survivors suffered from new-onset AF had increased incidence of IS within three months. New-onset AF was a mediator factor of IS in septicemia survivors of Asian population.

Regulation of the common carotid arterial blood flow by nicotinic receptors in the medulla of cats.

BACKGROUND AND PURPOSE: Actions of glutamate and serotonin on their respective receptors in the dorsal facial area (DFA) of the medulla are known to regulate common carotid arterial (CCA) blood flow in cats. Less is known about acetylcholine action on its nicotinic receptor (nAChR) subtypes in the DFA for regulation of CCA blood flow and this aspect was investigated. EXPERIMENTAL APPROACH: Nicotinic and muscarinic agonists and antagonists were microinjected into the DFA through a three-barrel tubing in anesthetized cats. RESULTS: CCA blood flow was dose-dependently increased by nicotine (a non-selective nAChR agonist) and choline (a selective alpha7-nAChR agonist). These effects of nicotine were attenuated by alpha-bungarotoxin (an alpha7-nAChR antagonist), methyllycaconitine (an alpha7-nAChR antagonist), mecamylamine (a relatively selective alpha3beta4-nAChR antagonist) and dihydro-beta-erythroidine (a relatively selective alpha4beta2-nAChR antagonist). The choline-induced flow increase was attenuated by alpha-bungarotoxin and mecamylamine, but not by dihydro-beta-erythroidine. Muscarinic agonists (muscarine and methacholine) and antagonist (atropine) affected neither the basal nor the nicotine-induced increase in the CCA blood flow. CONCLUSIONS AND IMPLICATIONS: Functional alpha7, alpha4beta2, and alpha3beta4 subunits of the nAChR appear to be present on the DFA neurons. Activations of these receptors increase the CCA blood flow. The present findings do not preclude the presence of other nAChRs subunits. Muscarinic receptors, if any, on the DFA are not involved in regulation of the CCA blood flow. Various subtypes of nAChRs in the DFA may mediate regulation of the CCA and cerebral blood flows.

Comparison of the effects of dihydroxyanthraquinone and adriamycin on the survival of cultured Chinese hamster cells.

Dihydroxyanthraquinone [1,4-dihydroxy-5,8-bis ((2-([(2-hydroxyethyl)amino)ethyl)amino))-9,10-anthracenedione (DHAQ) (NSC 279836)] is currently being tested as a cancer chemotherapeutic agent because of its structural similarity to Adriamycin (ADR) and other DNA-intercalating antibiotics. We have therefore studied the effect of DHAQ on the survival of cultured Chinese hamster cells in direct comparison to ADR. Both DHAQ and ADR produced cytotoxicity that was dependent upon the concentration and duration of drug exposure. For 1-hr pulse exposures of asynchronous populations of exponentially growing cells, a 5- to 10-fold greater concentration of ADR than of DHAQ was required to produce the same level of cell killing. There were also differences in the cell cycle age specificity demonstrated by treating at various times before or after selection of cells in mitosis. DHAQ produced the greatest cytotoxicity in cells treated while in G1 or G2; ADR was more effective on cells located in S phase or mitosis. Overall, DHAQ was found to be similar to ADR and other DNA-intercalating antibiotics with regard to the induction of cell lethality. The only differences were those of the concentration required to produce a certain level of effect and of the cell cycle phase specificities for maximum effect.

Effect of dihydroxyanthraquinone (NSC 279836) and thoracic irradiation on long-term survival of rats.

Dihydroxyanthraquinone (DHAQ; NSC 279836) is a recently synthesized compound that is structurally similar to Adriamycin and produces greater antitumor effects in murine model systems. We compared DHAQ to Adriamycin in rats, with and without irradiation of the chest at various intervals after drug treatment. A single injection of Adriamycin (1 mg/kg i.p.) had little effect on animal survival, even if combined with radiation (12 Gy 25 MV X-rays), greater than 90% being alive at 1 year. A single injection of DHAQ (3 mg/kg i.p.) was equally uneffective up to 200 days after treatment (survival, greater than 90%). However, between 200 and 370 days after treatment, all animals died, producing a median survival time of 280 days. Further, when DHAQ was combined with radiation, there was an increase in animal deaths between Days 300 and 200. For animals irradiated on Days 0, 43, and 93 after DHAQ treatment, only 50, 75, and 80%, respectively, survived to Day 200. All animals that survived past Day 200 subsequently died by 1 year, displaying the same kinetics of lethality as those animals that had received DHAQ only. A repeat experiment using DHAQ at 1 mg/kg produced similar results. Based on these findings, we conclude that DHAQ produces a long-term (greater than 200 days) toxicity in rats that is not detectable by short-duration toxicity screening. In addition, radiation enhances short-term (less than 200 days) lethality, with the degree of enhancement decreasing as the interval between drug and radiation is increased.

Enhancement of chemosensitivity by tyrphostin AG825 in high-p185(neu) expressing non-small cell lung cancer cells.

The HER-2/neu gene product, p185(neu), is a membrane-bound receptor with tyrosine kinase activity. High levels of p185(neu) is correlated with intrinsic chemoresistance of non-small cell lung cancer (NSCLC) cell lines. We investigated the effects of tyrphostin AG825, a selective tyrosine kinase inhibitor preferentially inhibiting HER-2/neu kinase, on the chemosensitivities and on the drug-induced cell cycle changes of NSCLC cell lines that expressed different levels of p185(neu). Compared to the low-p185(neu) expressing cell lines, we found that the high-p185(neu) expressing cell lines were more resistant to doxorubicin, etoposide, and cis-diamminedichloroplatinum(II) but more sensitive to AG825. AG825 was able to significantly enhance the chemosensitivities of the high-p185(neu) expressing cell lines, whereas it had little effect on the chemosensitivities of the low-p185(neu) expressing cells, with a few exceptions in which minor antagonistic effects were observed. Although high concentrations of AG825 could reduce the drug-induced G(2) arrest that was accompanied by the activation of phosphorylated p34(cdc2), we failed to find any remarkably differential effects of AG825 on drug-induced G(2), arrest and the accompanying phosphorylation status of p34(cdc2) of the high- and and the low-p185(neu) expressing cell lines. In summary, tyrphostin AG825 can enhance chemosensitivity in high- but not in low-p185(neu) expressing NSCLC cell lines. This differential effect cannot be explained by the alterations of drug-induced cell cycle changes by AG825. Our results provide a rationale to develop p185(neu)- specific tyrphostin and to test them in combination with anticancer agents in vivo and in clinical trials.

Isolation and characterization of a rat liver epithelial cell line resistant to the antiproliferative effects of transforming growth factor beta (type 1).

Rat liver epithelial cells resistant to the growth-inhibitory effects of transforming growth factor beta 1 (TGF-beta 1) were isolated after 3 h exposure to 1.5 micrograms/ml of N-methyl-N'-nitro-N-nitrosoguanidine followed by continuous treatment with 1 ng/ml TGF-beta 1 for 6 weeks. In comparison to the parental or N-methyl-N'-nitro-N-nitrosoguanidine-exposed rat liver epithelial cells (concentration causing 50% inhibition of the rate of DNA synthesis, 0.25 ng/ml), these cells were 10-fold more resistant to the antiproliferative effects of TGF-beta 1 and exhibited resistance to growth inhibition by a highly purified liver-derived growth inhibitor, recombinant human tumor necrosis factor, and transforming growth factor beta 2. Single cell cloning of these resistant cells led to the isolation of a nontransformed clonal cell population (clone 11) which maintained stable resistance in the absence of TGF-beta 1 treatment. Binding of 125I-labeled TGF-beta 1 to rat liver epithelial cells and clone 11 cells was similar. Clone 11 cells exhibited a 5-10-fold resistance to the cytotoxins Adriamycin and vinblastine as assessed by a clonogenic assay. This drug resistance was accompanied by an increase in the steady state levels of the mRNAs for multidrug resistance gene (MDR-1), glutathione S-transferase-P, TGF-beta 1, and c-myc genes. The data presented here suggest an association between resistance to the growth-inhibitory effects of TGF-beta 1- and MDR-1-mediated multidrug resistance.

Synthesis of simian virus 40 chromosomes in nuclear extracts from dihydroxyanthraquinone-treated cells.

The effect of dihydroxyanthraquinone (DHAQ), a new antitumor drug, on mammalian chromosome replication was investigated using simian virus 40 (SV40) as a model system. The maximum effect of inhibition on viral DNA synthesis was observed within 30-40 min after the addition of the drug. The extent of inhibition of viral DNA synthesis appeared to be directly related to the number of viral replicons which interact with DHAQ molecules in vivo. No apparent strand breakage of SV40 DNA was observed in infected cells treated with DHAQ ranging from 0.3 to 10 microM. However, strand breakage was induced upon cell lysis presumably by released nuclease. Repair of the damaged SV40 chromosomes in vitro resulted in the synthesis of completed supercoiled SV40 DNA. This repair synthesis was mostly confined to the region containing the replication origin of SV40 DNA as judged by the digestion of DNA with restriction endonucleases HindII and HindIII. Since SV40 DNA sequences close to the origin of replication are not complexed with histones to form a nucleosome structure, the results suggested that DHAQ may disturb chromosome structure by interacting preferentially to the nucleosome-free regions and causing the aberrant gene duplication and expression.

Accessory pathway and atrioventricular node reentrant tachycardia in elderly patients: clinical features, electrophysiologic characteristics and results of radiofrequency ablation.

OBJECTIVES: This study was designed to evaluate the clinical features, electrophysiologic characteristics and results of radiofrequency ablation in elderly patients with accessory atrioventricular (AV) pathways or AV node reentrant tachycardia. BACKGROUND: Radiofrequency ablation in elderly patients with paroxysmal supraventricular tachycardia has not been well described, and comparative study between elderly and younger patients is limited. METHODS: Electrophysiologic studies and radiofrequency ablation were performed in 92 elderly patients (45 with an accessory pathway, 47 with AV node reentrant tachycardia). RESULTS: The elderly patients had poorer electrophysiologic properties in accessory pathways and dual AV node pathways than those of younger patients. The success rate of radiofrequency ablation was similar in elderly and younger patients. However, elderly patients had more complications (14%) in left-sided accessory pathways. CONCLUSIONS: Radiofrequency ablation in elderly patients with supraventricular tachycardia was effective. However, it must be performed cautiously in those patients with left-sided accessory pathways.

Radiofrequency catheter ablation of common atrial flutter: comparison of electrophysiologically guided focal ablation technique and linear ablation technique.

OBJECTIVES: The purpose of this study was to study electrophysiologic characteristics and compare the electrophysiologically guided focal ablation technique and linear ablation technique in patients with common atrial flutter in a prospective randomized fashion. Background. Catheter ablation of the common atrial flutter circuit can be performed with different techniques. To date, these two techniques have not been compared prospectively in a randomized study. METHODS: Sixty patients with drug-refractory common atrial flutter were randomly assigned to undergo radiofrequency catheter ablation performed with the electrophysiologically guided focal ablation (Group I) or linear ablation technique (Group II). In Group I, radiofrequency energy was delivered to the site characterized by concealed entrainment with a short stimulus-P wave interval (<40 ms) and a postpacing interval equal to the atrial flutter cycle length. In Group II, continuous migratory application of radiofrequency energy was used to create two linear lesions in or around the inferior vena cava-tricuspid ring isthmus. Serial 24-h ambulatory electrocardiographic (Holter) and follow-up electrophysiologic studies were performed to assess recurrence of tachycardia and possible atrial arrhythmogenic effects. RESULTS: Successful elimination of the flutter circuit was achieved in 28 of 30 patients in Group I and 29 of 30 patients in Group II. More atrial premature beats and episodes of short run atrial tachyarrhythmias in the early period (within 2 weeks) after ablation were found in Group II. Recurrence rate (2 of 28 vs. 3 of 29) and incidence of new sustained atrial tachyarrhythmias (3 of 28 vs. 3 of 29) was similar in the two groups. Occurrence of recurrent atrial flutter and new sustained atrial tachyarrhythmias was related to associated cardiovascular disease and atrial enlargement in both groups. However, in Group II, the procedure time (104 +/- 17 vs. 181 +/- 29 min, p<0.01) were significantly shorter than those in Group I. CONCLUSIONS: Radiofrequency ablation of the common atrial flutter circuit was safe and effective with either the electrophysiologically guided focal ablation or linear ablation technique. However, the linear ablation technique was time-saving.

Modification of radiation and dihydroxyanthraquinone-induced cell lethality by cysteamine and N-ethylmaleimide.

The effect of alteration of sulfhydryl levels on the cell lethality induced by ionizing radiation and dihydroxyanthraquinone (DHAQ) was investigated in cultured Chinese hamster V79 cells. DHAQ produces a potentiation of radiation-induced cell lethality, both by increasing the slope and decreasing the shoulder of the survival curve. It has been suggested that DHAQ functions through the production of free radicals which then produce DNA strand breaks and crosslinks, resulting in cytotoxicity. If this mode of action predominates, then one would expect to be able to change the degree of cell kill by modifying conditions such that free radical processes were altered. This was accomplished by the addition of N-ethylmaleimide (NEM) or Cysteamine (CYS) to the culture medium during treatment with DHAQ. It was observed that the combination of DHAQ and NEM did not produce more cytotoxicity than would be expected from an additive interaction. Likewise, CYS did not reduce the cytotoxicity induced by DHAQ. When cells were treated with DHAQ and radiation plus either NEM or CYS, the resultant survival was consistent with an additive interaction between the potentiation of DHAQ for radiation-induced cell kill and the extra effect of NEM or CYS. These results indicate that alterations of sulfhydryl levels do not produce changes in the cytotoxicity induced by DHAQ, nor in the enhancement by DHAQ of radiation-induced lethality. More investigation is required before definite conclusions can be reached as to the mechanisms of action by which DHAQ, alone or in combination with ionizing radiation, induces mammalian cell lethality.